WO2025207473A1

WO2025207473A1 - Methods and compositions for diagnosing and selectively treating or preventing urinary tract infection and urobiome dysbiosis

Info

Publication number: WO2025207473A1
Application number: PCT/US2025/021083
Authority: WO
Inventors: Suzanne L. Groah; Rochelle E. Tractenberg
Original assignee: Georgetown University; MedStar Research Institute
Current assignee: Georgetown University; MedStar Research Institute
Priority date: 2024-03-26
Filing date: 2025-03-24
Publication date: 2025-10-02
Anticipated expiration: 2026-09-26

Abstract

A method of treating or preventing urobiome dysbiosis in a subject in need thereof is described. The method includes intravesicularly administering to the subject a therapeutically effective amount of two or more of an antimicrobial agent, and antispasmodic agent, and a live biotherapeutic product (LBP). Additional methods of determining the likelihood of symptomatic urinary tract infection (UTI) in a subject and selecting treatment for a UTI in a subject are described, as well as Live Biotherapeutic Product (LBP) compositions and the use thereof in methods for the treatment and/or prevention of UTI in a subject.

Description

METHODS AND COMPOSITIONS FOR DIAGNOSING AND SELECTIVELY TREATING OR PREVENTING URINARY TRACT INFECTION AND UROBIOME DYSBIOSIS [0001] This application claims priority from U.S. Provisional Application No. 63/569,755, filed March 26^th, 2024, the subject matter of which is incorporated herein by reference in its entirety. TECHNICAL FIELD [0002] This application also relates generally to the use of combination therapies in methods, systems, and kits for the treatment and/or prevention of urobiome dysbiosis in a subject in need thereof. This application relates generally to the use of combination therapies in methods, systems, and kits for the treatment and/or prevention of urobiome dysbiosis in a subject in need thereof, to methods of determining the likelihood of symptomatic urinary tract infection (UTI) in a subject and selecting treatment for a UTI in a subject, as well as compositions and methods for the treatment and/or prevention of UTI in a subject. BACKGROUND OF THE INVENTION [0003] People with SCI/D experience, on average, 2.5 episodes of urinary tract infection (UTI) annually. Since repeated exposures of bacteria to antibiotics leads to multi- drug resistant organisms (MDROs), it is likely that the frequent use of antibiotics for UTI is a driver of the increasing prevalence of infections with MDROs in the SCI/D population. This prevalence of MDROs among people with SCI/D represents a microcosm of the world-wide public health crisis of antibiotic resistance. As stated by the CDC, “antibiotic resistance is one of the biggest public health challenges of our time.” In the US alone, 2.8M people ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ Infections with resistant organisms are associated with longer hospital lengths of stay, increased mortality, and higher health care costs. With UTI persistently being the leading reason for rehospitalizations among people with SCI/D, infections with resistant organisms represent a contributor to elevated health care costs as well as mortality risk. Additionally, the cost to treat a UTI due to an extended-spectrum beta-lactamase (ESBL) organism is estimated to be 1.5 times greater than treating a non-ESBL pathogen. Thus, not only are people with SCI/D and UTI at greater risk of mortality due to MDROs, they are also likely to have higher costs as a result of UTI. These costs can only be expected to increase, as the rate of antibiotic resistant UTIs increases. Moreover, individuals with SCI/D and NLUTD experience lower urinary tract symptoms (LUTS) frequently, and these may be treated with antibiotics whether they represent UTI or not. [0004] The standard treatment approach to UTI (oral or intravenous antibiotics, typically targeting Gram-negative bacteria for 7-14 days) is flawed, as it is based on outdated and imprecise dogma that: (1) healthy urine is sterile (we now know that a urinary micr^^^^^^^^^^^^^^^^^^^^^^^^^^^ !^^"#$^^^^^^^^^^^^^^^^^^%^^^^^^^^^^^%^^^^^^^^^^^^^^^ &^^^^^^^'^^^^^^^^^ ^^^^%^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ culture (SUC) that preferentially grows E. coli over most other uropathogens and commensals. Also, after completion of antibiotic treatment, and due to the 'sterile urine' myth, restoring urobiome health post-antibiotics is not considered. Promoting resistance of the urobiome against repopulation with pathogens is also not considered, increasing risk of recurrent infections. As a result, treatment of UTIs in people with SCI/D is highly subjective, leading to overtreatment. Overtreatment with antibiotics has not improved UTI prevalence and has had the unwanted consequence of multidrug-resistant infections, frequently requiring subsequent re-treatment with broad-spectrum antibiotics. [0005] As noted above, the standard of care for UTI treatment (systemic antibiotics, guided by standard urine culture (SUC)) is flawed and contributes to overtreatment and antimicrobial resistance. Therefore, there remains a need for novel therapies capable of reducing antibiotic overtreatment and antimicrobial resistance. Such therapies will allow for the proper management of urobiome dysbiosis which can lead to lower urinary tract symptoms (LUTS) and/or UTI in individuals, such as those individuals with SCI/D, while simultaneously promoting antibiotic stewardship. [0006] UTI is the most common outpatient infection world-wide, and for people with spinal cord injury (SCI) and neurogenic lower urinary tract dysfunction (NLUTD), it is the most common infection, secondary condition, cause of emergency room visits, and infectious cause of hospitalization. UTI is not a single clinical entity but rather could be “uncomplicated” (UTI), “recurrent” (rUTI, 2+ in 6 months or 3+ annually), “catheter associated” (CA-UTI), and/or “complicated” (cUTI). [0007] Ronco et al. (2011) sought to improve diagnostic criteria for UTI in male patients with SCI using intermittent catheterization. In their 2009 Catheter-Associated UTI guidelines, the Infectious Diseases Society of America (IDSA) states that “the presence, absence, or degree of pyuria should not be used to differentiate catheter-associated asymptomatic bacteriuria from catheter-associated UTI.” The National Institute on Disability and Rehabilitation Research (NIDRR, 1992), Agency for Healthcare Research and Quality (AHRQ, 1999), the European Association of Urology (EAU) with other European and Asian urologic societies (2008, 2021, 2024) and the IDSA (2009) have all developed guidelines. However, neither consistent nor evidence-based guidelines exist. SUMMARY [0008] Embodiments described herein relate to combinations of an antimicrobial agent, and/or an antispasmodic agent, and/or a live biotherapeutic product (LBP) in therapeutic methods, systems, and kits for use in the treatment and/or prevention of urobiome dysbiosis in a subject in need thereof. [0009] In some embodiments, a method for the treatment and/or prevention of urobiome dysbiosis in a subject in need thereof. The method includes intravesicularly administering to the subject a therapeutically effective amount of two or more of an antimicrobial agent, an antispasmodic agent, and an LBP. [0010] In some embodiments, the antimicrobial agent and the LBP are administered sequentially to the subject. In some embodiments, the antimicrobial agent is administered to the subject for a period of time before the administration of the LBP. In some embodiments, the antimicrobial agent is administered to the subject about 1 hour, about 2 hours, about 4 hours, about 8 hours, about 12 hours, about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about 1 week, about 2 weeks or more before administration of the LBP. In some embodiments, the LBP can be administered to the subject about 1 hour, about 2 hours, about 4 hours, about 8 hours, about 12 hours, about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about 1 week, about 2 weeks or more after administration of the antimicrobial agent. [0011] In some embodiments, the LBP is administered concurrently with the antimicrobial agent for a period of time before the final administration of the antibiotic. In certain embodiments, the LBP can be administered concurrently with the antimicrobial agent for about 6 hours, about 12 hours, about 1 day, about 2 days, about 3 days, about 4 days or more. [0012] In particular embodiments, the LBP can include a probiotic treatment. The probiotic treatment can include a Lacticaseibacillus or a Lactobacillus probiotic bacterial species. In an exemplary embodiment, the Lacticaseibacillus probiotic bacterial species is Lacticaseibacillus rhamnosus GG (LGG). In some embodiments, the Lactobacillus probiotic bacterial species is Lactobacillus crispatus. [0013] In some embodiments, the antimicrobial agent is selected from the group consisting of an antibiotic, antiseptic, antiviral, antifungal, and antiparasitic agent. In some embodiments, the antimicrobial agent is an antibiotic. [0014] In some embodiments, the antibiotic can be selected from the group consisting of gentamicin, ampicillin, tobramycin, neomycin, polymyxin, amoxicillin/clavulanate, ceftriaxone, cephalexin, cefpodoxime, cefdinir, cefadroxil, ciprofloxacin, fosfomycin, levofloxacin, nitrofurantoin, trimethoprim/sulfamethoxazole, and combinations thereof. In an exemplary embodiment, the antibiotic can include gentamicin. [0015] In some embodiments, the antispasmodic agent can be selected from the group consisting of oxybutynin (Ditropan), tolterodine (Detrol), mirabegron (Myrbetriq), trospium, flavoxate, fesoterodine, darifenacin, solifenacin, hyoscyamine, and vibegron. In some embodiments, the antispasmodic agent includes oxybutynin (Ditropan). [0016] The antimicrobial agent, and/or the antispasmodic agent, and/or the LBP can be bladder instillation treatments that are intravesicularly administered to the subject. In some embodiments, the antimicrobial agent, and/or the antispasmodic agent, and/or the LBP can be self-administered to the subject. The subject can be provided preparation instructions for preparing and self-administering the antimicrobial agent, and/or the antispasmodic agent, and/or the LBP. [0017] In some embodiments, the subject has a spinal cord injury or disorder (SCI/D) and/or neurogenic lower urinary tract dysfunction (NLUTD). In some embodiments, the subject manages their bladder using intermittent catheterization (IC). In other embodiments, the subject manages their bladder using indwelling catheterization (IDC). In some embodiments, urobiome dysbiosis is a urinary tract infection (UTI). In some embodiments the subject does not have urobiome dysbiosis when treatment begins. [0018] In some embodiments, the urobiome dysbiosis in the subject is characterized by the overabundance of extended-spectrum beta-lactamase (ESBL) producing uropathogens in the lower urinary tract of the subject. The urobiome dysbiosis can be characterized by the subject having one or more lower urinary tract symptoms (LUTS). [0019] The antimicrobial agent, and/or the antispasmodic agent, and/or the LBP can be formulated in a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutically acceptable carrier can include citric acid and/or acetic acid. [0020] In particular embodiments, the therapeutically effective amount of two or more of a combination of the antimicrobial agent, the antispasmodic agent, and the LBP can include the amount required to reduce the abundance of native and/or uropathogenic bacterial species in the urinary tract and allow for colonization or recolonization of the LBP in the urinary tract of the subject. In some embodiments, the LBP is a probiotic bacterial species and colonization or recolonization of the probiotic bacterial species in the urinary tract of the subject is defined as the urobiome of the urinary tract having a probiotic bacterial density of about 10³ to about 10⁴ CFU/mL. In some embodiments, a therapeutically effective amount of two or more of the antimicrobial agent, antispasmodic agent, and LBP is the amount required to prevent, inhibit, or reduce a UTI and/or one or more LUTS in the subject. [0021] Other embodiments described herein relate to a system for selecting a treatment for urobiome dysbiosis in a subject. The system includes screening the subject for urobiome dysbiosis or the risk of developing urobiome dysbiosis and selecting a proper treatment if the subject has urobiome dysbiosis or the subject’s risk of developing urobiome dysbiosis exceeds a threshold, wherein the proper treatment includes the intravesical administration of a therapeutically effective amount of two or more of an antimicrobial agent, an antispasmodic agent, and a live biotherapeutic product (LBP) to the subject. [0022] The step of screening the subject for urobiome dysbiosis or the risk of developing urobiome dysbiosis comprises can include performing a urine test on a urine sample obtained from the subject. The urine test can determine the abundance of one or more uropathogenic bacterial species and/or the abundance of one or more probiotic bacterial species in the sample. In some embodiments, the urine test can include a urinalysis test. [0023] In some embodiments, the step of screening the subject for urobiome dysbiosis or the risk of developing urobiome dysbiosis can include providing a questionnaire to the subject, wherein the subject completes the questionnaire, and determining the presence of urobiome dysbiosis or the risk of developing urobiome dysbiosis in the subject based on the data from the questionnaire. The questionnaire can include questions related to the frequency of urinary symptoms, degree of severity of urinary symptoms, and/or impact of urinary symptoms in the subject. [0024] In some embodiments, the antimicrobial agent and the LBP are administered sequentially to the subject. In some embodiments, the antimicrobial agent is administered to the subject for a period of time before the administration of the LBP. In some embodiments, the antimicrobial agent is administered to the subject about 1 hour, about 2 hours, about 4 hours, about 8 hours, about 12 hours, about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about 1 week, about 2 weeks or more before administration of the LBP. In some embodiments, the LBP can be administered to the subject about 1 hour, about 2 hours, about 4 hours, about 8 hours, about 12 hours, about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about 1 week, about 2 weeks or more after administration of the antimicrobial agent. [0025] In some embodiments, the LBP is administered concurrently with the antimicrobial agent for a period of time before the final administration of the antimicrobial agent. In certain embodiments, the LBP can be administered concurrently with the antimicrobial agent for about 6 hours, about 12 hours, about 1 day, about 2 days, about 3 days, about 4 days or more. [0026] In particular embodiments, the LBP can include a probiotic treatment. The probiotic treatment can include a Lacticaseibacillus or a Lactobacillus probiotic bacterial species. In an exemplary embodiment, the Lacticaseibacillus probiotic bacterial species is Lacticaseibacillus rhamnosus GG (LGG). In some embodiments, the Lactobacillus probiotic bacterial species is Lactobacillus crispatus. [0027] In some embodiments, the antimicrobial agent is selected from the group consisting of an antibiotic, antiseptic, antiviral, antifungal, and antiparasitic agent. In some embodiments, the antimicrobial agent is an antibiotic. [0028] In some embodiments, the antibiotic can be selected from the group consisting of gentamicin, ampicillin, tobramycin, neomycin, polymyxin, amoxicillin/clavulanate, ceftriaxone, cephalexin, cefpodoxime, cefdinir, cefadroxil, ciprofloxacin, fosfomycin, levofloxacin, nitrofurantoin, trimethoprim/sulfamethoxazole, and combinations thereof. In an exemplary embodiment, the antibiotic can include gentamicin. [0029] In some embodiments, the antispasmodic agent can be selected from the group consisting of oxybutynin (Ditropan), tolterodine (Detrol), mirabegron (Myrbetriq), trospium, flavoxate, fesoterodine, darifenacin, solifenacin, hyoscyamine, and vibegron. In some embodiments, the antispasmodic agent includes oxybutynin (Ditropan). [0030] The antimicrobial agent, and/or the antispasmodic agent, and/or the LBP can be bladder instillation treatments that are intravesicularly administered to the subject. In some embodiments, the antimicrobial agent, and/or the antispasmodic agent, and/or the LBP can be self-administered to the subject. The subject can be provided preparation instructions for preparing and self-administering the antimicrobial agent, and/or the antispasmodic agent, and/or the LBP. [0031] In some embodiments, the subject has a spinal cord injury or disorder (SCI/D) and/or neurogenic lower urinary tract dysfunction (NLUTD). In some embodiments, the subject manages their bladder using intermittent catheterization (IC). In other embodiments, the subject manages their bladder using indwelling catheterization (IDC). In some embodiments, the urobiome dysbiosis is a urinary tract infection (UTI). In some embodiments the subject does not have urobiome dysbiosis when treatment begins. [0032] In some embodiments, urobiome dysbiosis in the subject is characterized by the overabundance of extended-spectrum beta-lactamase (ESBL) producing uropathogens in the lower urinary tract of the subject. The urobiome dysbiosis can be characterized by the subject having one or more lower urinary tract symptoms (LUTS). [0033] The antimicrobial agent, and/or the antispasmodic agent, and/or the LBP can be formulated in a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutically acceptable carrier can include citric acid and/or acetic acid. [0034] In particular embodiments, the therapeutically effective amount of two or more of the combination of the antimicrobial agent, the antispasmodic agent, and the LBP can include the amount required to reduce the abundance of native and/or uropathogenic bacterial species in the urinary tract and allow for colonization or recolonization of the LBP in the urinary tract of the subject. In some embodiments, the LBP is a probiotic bacterial species and colonization or recolonization of the probiotic bacterial species in the urinary tract of the subject is defined as the urobiome of the urinary tract having a probiotic bacterial density of about 10³ to about 10⁴ CFU/mL. In some embodiments, a therapeutically effective amount of two or more of the antimicrobial agent, the antispasmodic agent, and LBP is the amount required to prevent, inhibit, or reduce a UTI and/or one or more LUTS in the subject. [0035] Still other embodiments relate to kits for preventing and/or treating urobiome dysbiosis in a subject in need thereof. A kit includes one or more doses of a therapeutically effective amount of two or more of an antimicrobial agent, an antispasmodic agent, and a live biotherapeutic product (LBP), and equipment necessary to perform self-administered therapy for the antimicrobial agent, and/or the antispasmodic agent, and/or and LBP. [0036] In some embodiments, the kit can further include a plurality of urine diagnostic tests, wherein the plurality of urine diagnostic tests comprises equipment necessary to perform a self-administered urine diagnostic test for the detection of urobiome dysbiosis in the subject. The plurality of urine diagnostic tests can comprise a plurality of rapid screening urinalysis test strips and a plurality of urine collection containers. In some embodiments, the kit can further include information relating to the urine diagnostic test and instructions on how to perform the urine diagnostic test. [0037] In some embodiments, the kit further includes a plurality of UTI diagnostic tests. The plurality of UTI diagnostic tests can include equipment necessary to perform a self-administered UTI diagnostic test for the detection of a UTI in urine, wherein the plurality of UTI diagnostic tests comprise a plurality of leukocyte esterase and nitrite rapid screening urinary test strips and a plurality of urine collection containers. [0038] In some embodiments, the kits can further include information relating to the antimicrobial agent, and/or the antispasmodic agent, and/or LBP and instructions on how to select and self-administer the antimicrobial agent, and/or the antispasmodic agent, and/or LBP. In a particular embodiment, the antimicrobial agent is gentamicin, and the LBP is a Lacticaseibacillus rhamnosus GG (LGG) probiotic treatment. In other embodiments, the antimicrobial agent is gentamicin, and the LBP is a Lactobacillus crispatus probiotic treatment. In some embodiments, the antispasmodic agent includes oxybutynin (Ditropan). [0039] Additional Embodiments described herein relate to methods of determining the likelihood of symptomatic urinary tract infection (UTI) in a subject and selecting treatment for a UTI in a subject, as well as compositions and methods for the treatment and/or prevention of UTI in a subject. [0040] In some embodiments, a method of determining the likelihood of a symptomatic UTI in a subject is provided. The method includes screening the subject for one or more urinary symptoms. The urinary symptoms are selected from Action Needed, Bladder, Urine, and Other (previously referred to as Constitutional) urinary symptoms. The presence and/or absence of a combination of urinary symptoms correlates with a higher, moderate, low- moderate, lower, low, or lowest likelihood of symptomatic UTI. [0041] In some embodiments, the Action Needed symptoms are selected from the group consisting of bladder spasm frequency/discomfort, fever, increase in tone or spasticity, difficulty ambulating, difficulty thinking/mental fogginess/forgetfulness, mental slowing, dizziness, headache, flushing of chest/neck/face, bladder discomfort, sweating, autonomic dysreflexia, abdominal/suprapubic pain, and multiple sclerosis (MS) flare up. [0042] In some embodiments, the Bladder symptoms are selected from the group consisting of blood in urine, urinary urgency, incontinence/urine leakage, increase frequency of urination, sensation of urinary urgency, inability to fully empty bladder, weak urine stream, change in quality of pain when passing urine, change in quality of pain during catheterization, increase in catheterization frequency, blood clots in urine, and reduced urine volume/catheterization volume. [0043] In some embodiments, the Urine symptoms are selected from the group consisting of malodorous urine, dark urine, and cloudy/sediment in urine. [0044] In some embodiments, the Other symptoms are selected from the group consisting of increased fatigue/lethargy/weakness, chills, vomiting, loss of appetite, altered sleep patterns, muscle ache increase in positional pain, pain in the legs, change in bowel patterns, diarrhea, numbness/tingling in extremities, pain below level of injury, discharge/redness/sensitivity around catheter site, sense of burning in extremities/throughout the body, increase or decrease from normal blood pressure, malaise/feeling unwell, nausea, generalized abdominal discomfort or bloating, back pain, and irritability. [0045] In some embodiments, the subject is a subject managing their bladder via urinary voiding (V). The Action Needed symptoms are selected from the group consisting of bladder spasm frequency/discomfort, fever, increase in lower body tone or spasticity, difficulty ambulating, difficulty thinking/mental fogginess/forgetfulness, sweating, autonomic dysreflexia, and multiple sclerosis (MS) flare up. The Bladder symptoms are selected from the group of blood in urine, urinary urgency, incontinence/urine leakage, increase frequency of urination, sensation of urgency/empty bladder, inability to fully empty bladder, weak urine stream, and reduced urine volume/catheterization volume. The Urine symptoms are selected from malodorous urine, dark urine, and cloudy/sediment in urine. The Other symptoms are selected from the group consisting of increased fatigue/lethargy/weakness, chills, vomiting, malaise/feeling unwell, and nausea. [0046] In other embodiments, the subject is a subject managing their bladder via intermittent catheterization (IC). The Action Needed symptoms are selected from the group consisting of bladder spasm frequency/discomfort, fever, increase in lower body tone or spasticity, dizziness, headache, abdominal/suprapubic pain, autonomic dysreflexia, and difficulty thinking, mental fogginess, forgetfulness and confusion. The Bladder symptoms are selected from the group consisting of blood in urine, urinary urgency, incontinence/urine leakage, change in quality of pain when passing urine, change in quality of pain during catheterization, increase in catheterization frequency, and decreased catheter volume/catheterization volume. The Urine symptoms are selected from the group consisting of malodorous urine, dark urine, and cloudy/sediment in urine. The Other symptoms are selected from the group consisting of fatigue/lethargy/weakness, loss of appetite, altered sleep patterns, muscle ache increase in positional pain, pain in the legs, change in bowel patterns, malaise/feeling unwell, nausea, generalized abdominal discomfort or bloating, back pain, and irritability. [0047] In yet other embodiments, the subject is a subject managing their bladder via indwelling catheterization (IDC). The Action Needed symptoms are selected from the group consisting of bladder spasm frequency/discomfort, fever, increase in lower body tone or spasticity, flushing of chest/neck/face, bladder discomfort, sweating, autonomic dysreflexia, and abdominal/suprapubic pain. The Bladder symptoms are selected from the group consisting of blood in urine, urinary urgency, incontinence/urine leakage, and blood clots in urine. The Urine symptoms are selected from the group consisting of malodorous urine, dark urine, and cloudy/sediment in urine. The Other symptoms are selected from the group consisting of fatigue/lethargy/weakness, diarrhea, numbness/tingling in extremities, pain below level of injury, discharge/redness/sensitivity around catheter site, sense of burning in extremities/throughout the body, increase or decrease from normal blood pressure, generalized abdominal discomfort or bloating, back pain, and irritability. [0048] In some embodiments, the subject is determined to have a higher likelihood of symptomatic UTI by having at least one Action Needed symptom and one or more Bladder or Urine symptoms. In some embodiments, the subject is determined to have a moderate likelihood of symptomatic UTI by having either at least one Action Needed symptom and zero Bladder and Urine symptoms or zero Action Needed symptoms, one or more Bladder symptoms, and one or more Urine symptoms. In some embodiments, the subject is determined to have a low-moderate likelihood of symptomatic UTI by having zero Action Needed symptoms, 4 or more Bladder symptoms, and zero Urine symptoms. In some embodiments, the subject is determined to have a lower likelihood of symptomatic UTI by having either zero Action Needed symptoms, zero Bladder symptoms, one or more Urine symptoms, and one or more Other symptoms or zero Action Needed symptoms, 1-3 Bladder symptoms, zero Urine symptoms and zero Other symptoms. In some embodiments, the subject is determined to have a low likelihood of symptomatic UTI by having zero Action Needed symptoms, zero Bladder symptoms, zero Urine symptoms, and one or more Other symptoms. In some embodiments, the subject is determined to have a lowest likelihood symptomatic UTI by having: zero Action Needed symptoms, zero Bladder symptoms, zero Urine symptoms, and zero Other symptoms. [0049] In some embodiments, the subject has a neurogenic lower urinary tract dysfunction (NLUTD, also known as a neurogenic bladder (NB)). [0050] Other embodiments described herein relate to a method of selecting treatment for a UTI in a subject. The method includes screening the subject for one or more urinary symptoms, wherein the urinary symptoms selected from Action Needed, Bladder, Urine, and Other urinary symptoms, and wherein the presence and/or absence of a combination of urinary symptoms correlates with a higher, moderate, low-moderate, lower, low or lowest likelihood of symptomatic UTI. The method also includes selecting a UTI treatment based on the determined likelihood of symptomatic UTI in the subject. [0051] In some embodiments, the subject is determined to have a higher likelihood of symptomatic UTI, and the selected treatment includes administering to the subject a therapeutically effective amount of an antimicrobial agent and/or an antispasmodic. The antimicrobial agent can include an antibiotic agent. [0052] In some embodiments, the subject is determined to have a moderate, low- moderate, or lower likelihood of symptomatic UTI, and the selected treatment includes the administration of a therapeutically effective amount of a live biotherapeutic product (LBP) comprising Lacticaseibacillus rhamnosus and/or Lactobacillus crispatus. In some embodiments, the LBP is a bladder instillation treatment administered intravesicularly to the subject. The LBP treatment can be administered to the subject by a health care professional and/or self-administered by the subject. In some embodiments, the subject can be further provided preparation and/or administration instructions for the LBP treatment. [0053] In some embodiments, the subject is determined to have a low or a lowest likelihood of symptomatic UTI, and the treatment includes continued monitoring of urinary symptoms in the subject. The continued monitoring of urinary symptoms includes self- monitoring urinary symptoms by the subject. In some embodiments, the method further comprises providing to the subject instructions for self-monitoring urinary symptoms. [0054] In some embodiments, the Action Needed symptoms are selected from the group consisting of bladder spasm frequency/discomfort, fever, increase in tone or spasticity, difficulty ambulating, difficulty thinking/mental fogginess/forgetfulness, mental slowing. dizziness, headache, flushing of chest/neck/face, bladder discomfort, sweating, autonomic dysreflexia, abdominal/suprapubic pain and multiple sclerosis (MS) flare up. [0055] In some embodiments, the Bladder symptoms are selected from the group consisting of blood in urine, urinary urgency, incontinence/urine leakage, increase frequency of urination, sensation of urinary urgency, inability to fully empty bladder, weak urine stream, change in quality of pain when passing urine, change in quality of pain during catheterization, increase in catheterization frequency, blood clots in urine, and reduced urine volume/catheterization volume. [0056] In some embodiments, the Urine symptoms are selected from the group consisting of malodorous urine, dark urine, and cloudy/sediment in urine. [0057] In some embodiments, the Other symptoms selected from the group consisting of increased fatigue/lethargy/weakness, chills, vomiting, loss of appetite, altered sleep patterns, muscle ache increase in positional pain, pain in the legs, change in bowel patterns, diarrhea, numbness/tingling in extremities, pain below level of injury, discharge/redness/sensitivity around catheter site, sense of burning in extremities/throughout the body, increase or decrease from normal blood pressure, malaise/feeling unwell, nausea, generalized abdominal discomfort or bloating, back pain, and irritability. [0058] In some embodiments, the subject is a subject managing their bladder via urinary voiding (V) and the Action Needed symptoms are selected from the group consisting of bladder spasm frequency/discomfort, fever, increase in lower body tone or spasticity, difficulty ambulating, difficulty thinking/mental fogginess/forgetfulness, sweating, autonomic dysreflexia and multiple sclerosis (MS) ^^^^^^^^^^^^^^(^^^^^^^^^^^^^^^^^^^^ selected from the group of blood in urine, urinary urgency, incontinence/urine leakage, increase frequency of urination, sensation of urgency, inability to fully empty bladder, weak urine stream, and reduced urine volume)^^^^^^^^^*^^^^^^^^^^^^^^^^^^"^^^^^^^^^^^^^^^^^^ ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^+^^^^^^^^^^^^^^^^^^)^^^^^^^^^^^^^^^^^^^^^^^^^^^,^^^^^ symptoms are selected from the group consisting of increased fatigue/lethargy/weakness, chills, vomiting, malaise/feeling unwell, and nausea. [0059] In some embodiments, the subject is a subject managing their bladder via intermittent catheterization (IC) and the Action Needed symptoms are selected from the group consisting of bladder spasm frequency/discomfort, fever, increase in lower body tone or sp^^^^^^^^^^^^**^^^^^^^^^^^^^^^^^^^^^^^^^^)^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ Bladder symptoms are selected from the group consisting of blood in urine, urinary urgency, incontinence/urine leakage, change in quality of pain when passing urine, change in quality of pain during catheterization, increase in catheterization frequency, and decreased catheter ^^^^^^)^^^^^^^^^*^^^^^^^^^^^^^^^^^^"^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^%^^^^^^^^^^^^^^%^ of malodorous urine, dark urine, and cloudy/sediment in ^^^^^^^^^^^^^^^,^^^^^^^^^^^^^^^^^^ selected from the group consisting of fatigue/lethargy/weakness, loss of appetite, altered sleep patterns, muscle ache increase in positional pain, pain in the legs, change in bowel patterns, malaise/feeling unwell, nausea, generalized abdominal discomfort or bloating, back pain, and irritability. [0060] In some embodiments, the subject is a subject managing their bladder via indwelling catheterization (IDC) and the Action Needed symptoms are selected from the group consisting of bladder spasm frequency/discomfort, fever, increase in lower body tone or spasticity, flushing of chest/neck/face, bladder discomfort, sweating, autonomic ^^^^^^^^^^^^^^^^^^^^^^^^^^)^^^^^^^^^^^^^^^^^^^^^(^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ group consisting of blood in urine, urinary urgency, incontinence/urine leakage, and blood ^^^^^^^^^^^^^^^^^^^^"^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^%^^^^^^^^^^^^^^%^^^^^^^^^^^^^^^ ^^^^^^^^^^+^^^^^^^^^^^^^^^^^^)^^^^^^^^^^^^^^^^^^^^^^^^^^^,^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ the group consisting of fatigue/lethargy/weakness, diarrhea, numbness/tingling in extremities, pain below level of injury, discharge/redness/sensitivity around catheter site, sense of burning in extremities/throughout the body, increase or decrease from normal blood pressure, generalized abdominal discomfort or bloating, back pain, and irritability. [0061] In some embodiments, the subject has neurogenic lower urinary tract dysfunction (NLUTD). [0062] In some embodiments, the subject is determined to have a higher likelihood of symptomatic UTI, the subject having at least one Action Needed symptom and one or more Bladder or Urine symptoms. In some embodiments, the subject is determined to have a moderate likelihood of symptomatic UTI by having either at least one Action Needed symptom and zero Bladder or Urine symptoms or zero Action Needed symptoms, one or more Bladder symptoms, and one or more Urine symptoms. In some embodiments, the subject is determined to have a low-moderate likelihood of symptomatic UTI by having zero Action Needed symptoms, 4 or more Bladder symptoms, and zero Urine symptoms. In some embodiments, the subject is determined to have a lower likelihood of symptomatic UTI by having either zero Action Needed symptoms, zero Bladder symptoms, one or more Urine symptoms, and one or more Other symptoms or zero Action Needed symptoms, 1-3 Bladder symptoms, zero Urine symptoms and zero Other symptoms. In some embodiments, the subject is determined to have a low likelihood of symptomatic UTI by having zero Action Needed symptoms, zero Bladder symptoms, zero Urine symptoms, and one or more Other symptoms. In some embodiments, the subject is determined to have a lowest likelihood symptomatic UTI by having: zero Action Needed symptoms, zero Bladder symptoms, zero Urine symptoms, and zero Other symptoms. [0063] Yet other embodiments relate to a method of treating or preventing a UTI in a subject. The method includes administering to the subject a therapeutically effective amount of a live biotherapeutic product (LBP). The LBP includes Lacticaseibacillus rhamnosus and Lactobacillus crispatus. In some embodiments, the therapeutically effective amount is the amount required to reduce the frequency, degree of severity and/or impact of urinary symptoms on the subject. [0064] In some embodiments, the Lacticaseibacillus rhamnosus is Lacticaseibacillus rhamnosus GG (LGG). In some embodiments, the Lactobacillus crispatus is Lactobacillus crispatus CTV-05, Lactobacillus crispatus SJ-3C and/or Lactobacillus crispatus 262-1. [0065] In some embodiments, the LBP is an LBP bladder instillation treatment administered intravesicularly to the subject. In some embodiments, the LBP is administered to the subject by a health care professional. In some embodiments, the LBP is self- administered by the subject. In some embodiments, the method further includes providing to the subject preparation instructions for the LBP treatment. [0066] In some embodiments, the method includes administering to the subject one or more additional therapeutic agents. The one or more therapeutic agents are selected from the group consisting of an additional probiotic bacterial species (e.g., a Lacticaseibacillus or Lactobacillus species), an antimicrobial agent and an antispasmodic agent. In some embodiments, the antimicrobial agent is an antibiotic agent. [0067] In some embodiments, the subject has NLUTD. In some embodiments, the subject has a spinal cord injury or disorder (SCI/D), spina bifida, and/or multiple sclerosis. In some embodiments, the UTI is a Catheter-Associated Urinary Tract Infection (CAUTI). [0068] In some embodiments, the subject manages their bladder using urinary voiding (V). In some embodiments, the subject manages their bladder using intermittent catheterization (IC). In some embodiments, the subject manages their bladders using indwelling catheterization (IDC). [0069] In some embodiments, the subject is determined to have a moderate, low- moderate, or lower likelihood of symptomatic UTI, wherein the likelihood of symptomatic UTI is determined in the subject according to a method described herein. [0070] Yet still other embodiments described herein relate to a pharmaceutical composition for the treatment or prevention of a UTI. The composition includes a live biotherapeutic product (LBP), wherein the LBP includes a combination of Lacticaseibacillus rhamnosus and Lactobacillus crispatus. [0071] In some embodiments, the Lacticaseibacillus rhamnosus is Lacticaseibacillus rhamnosus GG (LGG). In some embodiments, the Lactobacillus crispatus is Lactobacillus crispatus CTV-05, Lactobacillus crispatus SJ-3C and/or Lactobacillus crispatus 262-1. [0072] In some embodiments the composition further includes a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutically acceptable carrier is formulated for intravesical, topical, intravaginal, and/or intraurethral administration. [0073] In some embodiments, the composition is a dried formulation. In some embodiments, the composition is in a single dose form appropriate for intravesical, topical, intravaginal, and/or intraurethral administration. BRIEF DESCRIPTION OF THE FIGURES [0074] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate some embodiments disclosed herein, and together with the description, serve to explain principles of the disclosed embodiments. [0075] Figs.1(A-B) provides a graphical illustration showing the relative abundance of genera detected by 16S sequence in male and female NB patients and controls. [0076] Fig.2 provides a graphical illustration showing that the mouse urobiome from 25 female C57BL/6 mice. Colors in legend correspond to most common taxa. Less common taxa not defined. [0077] Fig.3 provides images from immunofluorescent staining of 9-day old bladder organoids. A single membrane was stained with DAPI (blue) and WGA633 (red) and imaged using z-stack protocol with confocal at 40X. Top-view of the organoids (left image) shows 6 areas of differentiation (outlined in yellow, middle image) in which WGA633 staining is more concentrated on the apical surface of GAG-expressing, large, differentiated umbrella cells (yellow arrows, middle) compared to bladder cells displaying a smaller, intermediate cell morphology (white arrows, middle). Areas with umbrella cells are raised, creating a 3D structure which is evident when moving down the z-axis to reveal 3-4 layers of intermediate and basal cell layers protected from WGA633 staining (areas of blue, right image) in the larger organoid structures. [0078] Figs.4(A-C) provide images of the ultrasound-guided aspiration of a mouse bladder. [0079] Fig.5 provides a flow diagram of a randomized clinical trial. [0080] Fig.6 provides a flow diagram illustrating an example method and decision tree for determining the likelihood of a symptomatic UTI in a subject and for selecting the appropriate treatment. DETAILED DESCRIPTION [0081] The following description of various embodiments is exemplary and explanatory only and is not to be construed as limiting or restrictive in any way. Other embodiments, features, objects, and advantages of the present teachings will be apparent from the description and accompanying drawings, and from the claims. [0082] For convenience, certain terms employed in the specification, examples, and appended claims are collected here. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. [0083] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges, and are also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention. [0084] The articles "a" and "an" are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, "an element" means one element or more than one element. [0085] The terms "comprise," "comprising," "include," "including," "have," and "having" are used in the inclusive, open sense, meaning that additional elements may be included. The terms "such as", "e.g.,", as used herein are non-limiting and are for illustrative purposes only. "Including" and "including but not limited to" are used interchangeably. [0086] The term "or" as used herein should be understood to mean "and/or", unless the context clearly indicates otherwise. [0087] As used herein, the term "about" or "approximately" refers to a quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length that varies by as much as 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2% or 1% to a reference quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length. In one embodiment, the term "about" or "approximately" refers a range of quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length ± 15%, ± 10%, ± 9%, ± 8%, ± 7%, ± 6%, ± 5%, ± 4%, ± 3%, ± 2%, or ± 1% about a reference quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length. [0088] The terms "treatment," "treating," and the like are art-recognized and include inhibiting a disease, disorder, or condition in a subject, e.g., ^^^^^^^%^^^^^^^^%^^^^^^^^^^ relieving the disease, disorder or condition, e.g., causing regression of the disease, disorder and/or condition. Treating the disease or condition includes ameliorating at least one symptom of the particular disease or condition, even if the underlying pathophysiology is not affected. In certain embodiments, the term “treatment” can include inhibiting or preventing urobiome dysbiosis in a subject from progressing to one or more lower urinary tract symptoms (LUTS) and/or a urinary tract infection (UTI). In other embodiments, the term “treatment” can include inhibiting or preventing UTI. [0089] The term "preventing" is art-recognized and includes stopping a disease, disorder or condition from occurring in a subject, which may be predisposed to and/or at risk of developing the disease, disorder and/or condition but has not yet been diagnosed as having it. Preventing a condition related to a disease includes stopping the condition from occurring after the disease has been diagnosed but before the condition has been diagnosed. [0090] The term "pharmaceutical composition" refers to a formulation containing the disclosed agents in a form suitable for administration to a subject. For example, live biotherapeutic products (LBPs), such as probiotic bacterial preparations, can be provided in lyophilized form. This is achieved by freeze-drying, a process that provides dry powdered products using low temperatures and pressures. In a preferred embodiment, the pharmaceutical composition is in bulk or in unit dosage form. The unit dosage form is any of a variety of forms, including, for example, a suppository, a capsule, an IV bag, a tablet, or a vial. The quantity of active ingredient (e.g., an antibiotic compound or an LBP) in a unit dose of a composition is an effective amount and is varied according to the particular treatment involved. One skilled in the art will appreciate that it is sometimes necessary to make routine variations to the dosage depending on the age and condition of the patient. The dosage will also depend on the route of administration. A variety of routes are contemplated, including, but not limited to, intravesicular, vaginal, oral, parenteral, intravenous, and the like. In a preferred embodiment, the active compound(s) are mixed under sterile conditions with a pharmaceutically acceptable carrier, and with any additives, preservatives, buffers, or propellants that are required. The term “intravesical administration” is used in its conventional sense to mean direct drug/therapeutic delivery to the bladder. [0091] The phrase "pharmaceutically acceptable" is art-recognized. In certain embodiments, the term includes compositions, polymers and other materials and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio. [0092] The phrase "pharmaceutically acceptable carrier" is art-recognized, and includes, for example, pharmaceutically acceptable materials, compositions, or vehicles, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material, involved in carrying or transporting any subject therapeutic agent or combination thereof from one organ, or portion of the body, to another organ, or portion of the body. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of a subject agent and not injurious to the patient. In certain embodiments, a pharmaceutically acceptable carrier is non-pyrogenic. Some examples of materials which may serve as pharmaceutically acceptable carriers include: (1) sugars, such as lact^^^^^%^^^^^^^^^^^^^^^^^^^^ !^^^^^^^^^^^^^^^^^ ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ -^^^^^^^^^^^^^^%^^^^^^^^ ^^^ ^^^^^^ .^^%^^^^^^^^ /^^^^^^^^ 0^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ 1^^^^^^^^ such as peanut oil, cottonseed oil, sunflower oil, sesame oil, olive oil, corn oil and soybean ^^^^^ 2^^^%^^^^^^^^^^^^^^^^^^^^^^^^^^%^^^^^^^ 22^^^^^^^^^^^^^^^^^^^%^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^^^^^^^^^^^^^^^^^%^^^^^^^ 2!^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ 2^^^^%^^^^ 2-^^ ^^^^^^^^%^^%^^^^^^^^^^^^^^^^%^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ 2^^^^^%^^^^^^^^^^^ (16) pyrogen-^^^^^^^^^^^^ 2/^^^^^^^^^^^^^^^^^^^ 20^^3^^%^^4^^^^^^^^^^^^ 21^^^^^^^^^^^^^^^^^ !^^^ ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ !2^^^^^^^^^^^-toxic compatible substances employed in pharmaceutical formulations. [0093] As used herein, the term “excipient” and “inactive excipient” are used interchangeably and refer to inert substances formulated alongside the active ingredient of a medication, included for the purpose of long-term stabilization, providing bulk to the powder formulation (thus often referred to as “bulking agents,” “fillers,” or “diluents”), or to confer a therapeutic enhancement on the active ingredient in the final dosage form, such as facilitating drug absorption, reducing viscosity, or enhancing solubility. Examples of excipients include, without limitation, maltodextrin, starch, pre-gelatinized starch, microcrystalline cellulose, calcium carbonate, dicalcium phosphate, colloidal SiO2, Pharmasperse, mannitol, xylitol, trehalose, lactose, sucrose, polyvinyl pyrrolidone, crospovidone, glycine, magnesium stearate, sodium stearyl fumarate, cyclodextrins and derivatives and mixtures thereof. [0094] The term “dry composition” as used herein refers to a composition from which moisture has been removed. Drying or desiccation techniques include, e.g., heating (e.g., sublimation), application of low pressure or vacuum, lyophilization (i.e., freeze drying), and combinations thereof. Compositions are commonly desiccated for easy storage and transport. [0095] The term “lyophilization” as used herein refers to the process of freezing a substance and then reducing the concentration of water, by sublimation and/or evaporation to levels which do not support biological or chemical reactions. [0096] The terms "prophylactic” or “therapeutic" treatment is art-recognized and includes administration to the subject of one or more of the subject combinations of therapeutic agents or therapies. If it is administered prior to clinical manifestation of the unwanted condition (e.g., disease or other unwanted state of the subject such as, but not limited to, lower urinary tract symptoms (LUTS)), then the treatment is preventative or prophylactic, i.e., it protects the subject against developing the unwanted condition, whereas if it is administered after manifestation of the unwanted condition, the treatment is therapeutic (i.e., it is intended to diminish, reduce, ameliorate, or stabilize the existing unwanted condition, symptoms, or side effects thereof). [0097] The terms "therapeutic agent", "drug", "medicament" and "bioactive substance" are art-recognized and include molecules and other agents that are biologically, physiologically, or pharmacologically active substances that act locally or systemically in a patient or subject to treat a disease or condition. The terms include without limitation pharmaceutically acceptable salts thereof and prodrugs. Such agents may be acidic, basic, or ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^es capable of ^^^^^%^^^^^^^^^%^^^^^^^^^^^^^^^^^^^^%^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^+^^ that are biologically activated when administered into a patient or subject. [0098] The phrase "therapeutically effective amount" or “pharmaceutically effective amount” is an art-recognized term. In certain embodiments, the term refers to an amount of a therapeutic agent or combination of therapeutic agents that produces some desired effect at a reasonable benefit/risk ratio applicable to any medical treatment. In certain embodiments, the term refers to that amount necessary or sufficient to eliminate, reduce or maintain a target of a particular therapeutic regimen. The therapeutically effective amount may vary depending on such factors as the disease or condition being treated, the particular targeted constructs being administered, the size of the subject or the severity of the disease or condition. One of ordinary skill in the art may empirically determine the effective amount of a particular agent, or combination of agents, without necessitating undue experimentation. [0099] A “urinary tract infection” (UTI), as defined herein, is an infection of any part of the urinary tract. The urinary tract includes the kidneys, the bladder, the urethra, and the ureters. Infection of the urinary tract typically results in a variety of symptoms, depending on the specific site of infection. For example, infection of the kidneys (e.g., acute pyelonephritis) can result in upper back and side pain, high fever, shaking and chills, nausea, and vomiting. Infection of the bladder (e.g., cystitis) can result in pelvic pressure, lower abdomen discomfort, frequent and painful urination, and blood in the urine. Infection of the urethra (e.g., urethritis) typically includes a burning sensation associated with urination. For a febrile UTI, a fever will be present, and possibly other associated symptoms such as shaking and chills as well. UTI typically refers to a bacterial infection. The bacteria can be gram-negative bacteria, or the bacterial can be gram-positive bacteria. For example, the bacteria can be one or more of E. coli, Pseudomonas, Enterococcus, Enterobacter, Klebsiella, or Proteus mirabilis. The majority (80-85%) of bacterial urinary tract infections are caused by E. coli. However, a urinary tract infection can also occur as a result of infection by pathogens other than bacteria. For example, urinary tract infections can also be caused by viruses and fungus. Examples of urinary viral infections include those by BK virus, cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Fungal infection is commonly caused by infection by fungi of the genus Candida. [00100] As used herein, the term “symptomatic UTI” refers to a microorganism, e.g., bacteria and fungi, infection that causes clinical signs and/or laboratory evidence of a UTI in a subject. [00101] As used herein, the term “uncomplicated UTI”, typically refers to an acute, sporadic or recurrent lower (uncomplicated cystitis) and/or upper (uncomplicated pyelonephritis) UTI, limited to non-pregnant women with no known relevant anatomical and functional abnormalities within the urinary tract or comorbidities. [00102] As used herein, the term “complicated UTI (cUTI)” typically refers to all UTIs which are not defined as uncomplicated. In particular, cUTIs can include all UTIs in a patient with an increased chance of a complicated course: i.e. all men, pregnant women, patients with relevant anatomical or functional abnormalities of the urinary tract, indwelling urinary catheters, renal diseases, and/or with other concomitant immunocompromising diseases for example, diabetes. In certain embodiments, a cUTI can occur in an individual in whom factors related to the host (e.g. underlying diabetes or immunosuppression) or specific anatomical or functional abnormalities related to the urinary tract (e.g. obstruction, incomplete voiding due to detrusor muscle dysfunction) are believed to result in an infection that will be more difficult to eradicate than an uncomplicated infection. [00103] As used herein, the term “likelihood of a symptomatic UTI”, can refer to the probability or percent possibility of a subject having a symptomatic UTI, for example, in comparison with a control or threshold value. [00104] As used herein, the term “urobiome dysbiosis”, refers to an imbalance in microbial diversity, including differences in the abundance and species richness, in the microenvironments along the urinary tract, and in particular an imbalance of uropathogenic species diversity associated with lower urinary tract symptoms (LUTS) and/or urinary tract infections (UTIs). As used herein “risk of urobiome dysbiosis” can refer to the likelihood or percent possibility of having urobiome dysbiosis, for example, in comparison with a control or threshold value. [00105] The term “live biotherapeutic product (LBP)” and “live biotherapeutic products (LBPs)” as used herein can be interchangeably and refer to a biological product that includes live microorganisms, e.g., bacteria and yeasts, which is applicable to the prevention, ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^5^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ transplant or gene therapy agent. In some embodiments, therapeutics based on LBPs can have a multifactorial mode of action (MOA) and are not intended to reach the systemic circulation and target distant organs, tissues, or receptors. LBPs typically involve a direct interaction with the local ecosystem of the host by modulating the native microbiota, for example by inhibiting pathogens, modulating the activity of the mucosal immune system and/or the nervous system and by producing active molecules. All of those may occur individually or simultaneously, leading to further biological effects within the host subject. In some embodiments, the LBP is a therapeutic composition that will undergo or has undergone clinical regulatory approval. [00106] The term “Lactobacillus” as used herein refers to a genus of bacteria that are Gram-positive facultative anaerobic bacteria, characterized by the ability to produce lactate (lactic acid) from carbohydrate sources such as glucose. These bacteria may be present in food products or be commensal organisms that colonize the vaginal or gastrointestinal mucosa. [00107] The terms “antimicrobial” and “antimicrobial agent” as used herein can be used interchangeably and mean any natural or synthetic substance that kills, destroys, inhibits and/or prevents the growth, colonization, and multiplication of organisms and that is safe for therapeutic use. The term “organism” includes, but is not limited to, microorganisms, bacteria, undulating bacteria, spirochetes, spores, spore-forming organisms, gram-negative organisms, gram-positive organisms, yeasts, fungi, molds, viruses, aerobic organisms, anaerobic organisms, parasitic organism, and mycobacteria. [00108] The terms “antispasmodic” and “antispasmodic agent” as used herein can be used interchangeably and mean, in a general sense, an agent that reduces, prevents, or relieves muscle spasms of muscle, in particular smooth muscle spasms such as bladder smooth muscle spasms. Unless otherwise indicated, the term “antispasmodic” is intended to encompass antispasmodic agents as further disclosed herein, and salts, enantiomers, esters, amides, prodrugs, metabolites, and derivatives thereof. [00109] The terms "probiotic" and "probiotics" as used herein can be used interchangeably and mean one or more natural, cultured, purified, genetically altered, and/or ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ bacteria^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ that could confer health benefits on the host subject when administered in adequate amounts, more specifically, that beneficially affect a host by improving its urinary system microbial balance, leading to effects on the health or well-being of the host, e.g., a reduction of problematic urinary symptoms related to a urobiome dysbiosis and/or a urinary tract infection. The probiotics of the present invention can be viable or non-viable when administered and/or when reaching the desired site of administration. The probiotics of the present invention can be administered together as a blend or mixture in a single dosage form or can be administered in separate dosage forms at separate times. [00110] As used herein, the term “antibiotic” refers to a natural or synthetic substance that has the capacity to inhibit the growth of, or to kill other microorganisms. As used herein, the term “microorganism” refers to prokaryotic and eukaryotic cells, which grow as single cells, or when growing in association with other cells, do not form organs (e.g., microorganisms include bacteria, yeast, molds, and fungi). [00111] The term "colonization" of a host organism as used herein refers to non-transient residence of bacteria or other microscopic organisms. The term “recolonization” as used herein can refer to restoration or repopulation of a previously colonizing microbial species in a region or habitat, such as the urobiome or a subject. [00112] The terms “subject” and “patient” are used interchangeably and refer to mammals such as human patients and non-human primates, as well as experimental animals such as rabbits, dogs, cats, rats, mice, and other animals. Accordingly, the term “subject” or “patient” as used herein can refer to any mammalian patient or subject to which combination therapy of two or more of an antimicrobial agent, an antispasmodic agent, and an LBP of the invention can be administered. Subjects of the present invention can include those experiencing, or at risk, of urobiome dysbiosis and/or related lower urinary tract symptoms (LUTS). In some embodiments, the term “subject” or “patient” as used herein means any mammalian patient or subject for which the likelihood of a symptomatic UTI can be determined for, treatment for UTI selected, and/or to which therapeutic for the treatment or prevention of a UTI can be administered. Subjects of the present invention include those experiencing, or at risk or having a likelihood, of UTI and/or related lower urinary tract symptoms (LUTS). For example, a subject may not have a UTI when practice of a method described herein begins. [00113] As used herein, the term “synergistic effect” refers to a larger therapeutic effect of two or more of an antimicrobial agent, an antispasmodic agent, and LPB combination therapy disclosed in comparison to the effect predicted from the sum of each therapeutic agent/treatment alone. [00114] Dysbiosis of the healthy urobiome reflects imbalances between uropathogens and protective microorganisms in the urobiome and is associated with various clinical states. Lower urinary tract symptoms (LUTS) usually represent a urinary tract infection (UTI) in a subject and typically, UTI treatment focuses on antibiotic treatment without consideration of the urobiome and urobiome restoration post-antibiotics. However, inattention to the restoration of the urobiome in a subject after antibiotic treatment can allow re-population of pathogens and permit reinfection, or urobiome dysbiosis, that cannot combat pathogens. [00115] It has been shown that successful colonization of the bladder with a live biotherapeutic product (LBP), such as the Lacticaseibacillus probiotic bacterial species Lacticaseibacillus rhamnosus Gorbach-Goldin (LGG), reduces urobiome dysbiosis and results in resistance to UTI and other LUTS. It is contemplated that intravesicular administration of combination therapies that include two or more of an antimicrobial agent, an antispasmodic agent, and an LBP can provide therapeutic benefits to subjects experiencing urobiome dysbiosis. In particular, it is believed that inhibiting uropathogenic bacterial burden and activity via intravesicular administration of an antimicrobial agent (e.g., an antibiotic), and/or an antispasmodic agent, prior to, or concurrently with, intravesicular administration with a LBP, can improve colonization of the protective LBP in the lower urinary tract, thereby restoring and reconstituting a healthy urobiome capable of protecting the subject against uropathogenic associated LUTS and prevents future UTIs. [00116] Accordingly, embodiments described herein relate to a method of treating or preventing urobiome dysbiosis in a subject in need thereof. The method includes intravesicularly administering to the subject a therapeutically effective amount of two or more of an antimicrobial agent, antispasmodic agent, and an LBP. [00117] LBPs useful in a combination therapy described herein may include one or more probiotics. The probiotic(s) of a combination therapy can be any biological product that includes microorganisms, e.g., beneficial symbiotic bacteria and yeasts, which are applicable to the prevention and or treatment of urobiome dysbiosis in a subject. Typically, the probiotics of the present invention are viable when administered and when reaching the desired site of administration. The probiotics of the present invention can be administered together as a blend or mixture in a single dosage form or can be administered in separate dosage forms at separate times. In addition, as the probiotics are taken via intravesicular administration, such as bladder instillation, the probiotics are capable of successfully colonizing the lower urinary tract. [00118] In some embodiments, probiotic treatment can include administering to the subject a probiotic bacteria species commonly found in the urobiome of a subject who does not have urobiome dysbiosis, a high or elevated risk of developing urobiome dysbiosis, and/or symptoms (e.g., LUTS) related to or associated with urobiome dysbiosis. [00119] Non-limiting examples of probiotics useful with the present invention include bacteria selected from the group consisting of Bifidobacterium, Lactobacillus, Lacticaseibacillus, and Streptococcus. Particular non-limiting examples of probiotics useful herein include Lacticaseibacillus rhamnosus, (formerly known as Lactobacillus rhamnosus), Lacticaseibacillus casei (formerly known as Lactobacillus casei), Lactobacillus crispatus, Lactobacillus planetarium, Lactobacillus salivarius, Lactobacillus rueteri, Lactobacillus bulgaricus, Lactobacillus sporogenes, Lactococcus lactis, Bifidophilus infantis, Streptococcus thermophilous, Bifodophilus longum, Bifidobacteria bifidus, Arthrobacter agilis, Arthrobacter citreus, Arthrobacter globiformis, Arthrobacter leuteus, Arthrobacter simplex, Azotobacter chroococcum, Azotobacter paspali, Azospirillum brasiliencise, Azospriliium lipoferum, Bacillus brevis, Bacillus macerans, Bacillus pumilus, Bacillus polymyxa, Bacillus subtilis, Bacteroides lipolyticum, Bacteroides succinogenes, Brevibacterium lipolyticum, Brevibacterium stationis, Kurtha zopfil, Myrothecium verrucaris, Pseudomonas calcis, Pseudomonas dentrificans, Pseudomonas flourescens, Pseudomonas glathei, Phanerochaete chrysosporium, Streptmyces fradiae, Streptomyces cellulosae, Stretpomyces griseoflavus, Bacillus laterosporus, Bacillus bifidum, Bacillus laterosporus, and combinations thereof. [00120] In certain embodiments, probiotics for the present invention are non-pathogenic, and/or non-fever-inducing bacteria, such as Lacticaseibacillus or Lactobacillus bacteria. In particular embodiments, the probiotic is Lacticaseibacillus rhamnosus strain Gorbach-Goldin (LGG). [00121] Antispasmodic agents for use in a combination therapy described herein can include anticholinergic agents. Exemplary anticholinergic agents for use in a method described herein can include, but are not limited to, oxybutynin (Ditropan), tolterodine (Detrol), flavoxate, fesoterodine, darifenacin, trospium, solifenacin, propantheline, duloxetine, dicyclomine, phenylpropanolamine, and hyoscyamine. In particular embodiments, the antispasmodic agent can be oxybutynin or a pharmaceutically acceptable salt thereof. For example, oxybutynin salts include acetate, bitartrate, citrate, edetate, edisylate, estolate, esylate, fumarate, gluceptate, gluconate, glutamate, hydrobromide, hydrochloride, lactate, malate, maleate, mandelate, mesylate, methylnitrate, mucate, napsylate, nitrate, pamoate, pantothenate, phosphate, salicylate, stearate, succinate, sulfate, tannate and tartrate. [00122] In some embodiments, the antispasmodic agent can include a beta-3 adrenergic agonist. Exemplary beta-3 adrenergic receptor agonists can include mirabegron (Myrbetriq) and vibegron. [00123] Antimicrobial agents for use in a combination therapy described herein can include antibiotics, antiseptics, antivirals, antifungals, antiparasitics, and combinations thereof. Antimicrobials typically kill microorganisms and/or prevent their growth by targeting key steps in cellular metabolism such as the synthesis of biological macromolecules, the activity of cellular enzymes, or cellular structures, such as the cell wall and cell membranes. [00124] In particular embodiments, the antimicrobial agent can include one or more antibiotics. The antibiotic agent for use in a combination therapy for the treatment or prevention of urobiome dysbiosis described herein can include any antibiotic effectively used for treating uropathogenic related urinary tract symptoms and/or urinary tract infections. In some embodiments, the antibiotic is selected from the group consisting of gentamicin, ampicillin, tobramycin, neomycin, polymyxin, amoxicillin, amoxicillin/clavulanate, ceftriaxone, cephalexin, cefpodoxime, cefdinir, cefadroxil, ciprofloxacin, fosfomycin, levofloxacin, nitrofurantoin, trimethoprim/sulfamethoxazole, and combinations thereof, such as trimethoprim/sulfamethoxazole and neomycin/polymyxin. In particular embodiments, the antibiotic agent is selected from the group consisting of gentamicin, tobramycin, colistin, neomycin, polymyxin and combinations thereof, such as neomycin/polymyxin. [00125] In exemplary embodiments, the antibiotic is gentamicin. Gentamicin is the most commonly studied intravesical antibiotic and when administered intravesicularly, it has been shown to be safe, tolerated, and effective for recurrent urinary tract infections (UTIs) in people with neurogenic lower urinary tract dysfunction (NLUTD) having little to no systemic absorption, nor nephro- or oto-toxicity (as with intravenous administration). [00126] In some embodiments, an antimicrobial agent, and/or an antispasmodic agent, and/or an LBP can be administered in a combinatorial therapy or combination therapy. The phrase “combinatorial therapy” or “combination therapy” embraces the administration of two or more antimicrobial agent (s), and/or antispasmodic agent(s), and/or LBP(s) described herein as part of a specific treatment regimen intended to provide beneficial effect from the co-action of these therapeutic agents. Administration of these therapeutic agents in combination typically is carried out over a defined period (usually minutes, hours, days or weeks depending upon the combination selected). [00127] “Combinatorial therapy” or “combination therapy” is intended to embrace administration of these therapeutic agents in a sequential manner, that is, wherein each therapeutic agent is administered at a different time, as well as administration of at least these two therapeutic agents, in a substantially simultaneous manner. Substantially simultaneous administration can be accomplished, for example by administering to the subject an individual dose having a fixed ratio of each therapeutic agent or in multiple, individual doses for each of the therapeutic agents. Sequential or substantially simultaneous administration of each therapeutic agent can be achieved by any appropriate route including, but not limited to, intravesicular routes, oral routes, intravenous routes, intramuscular routes, direct absorption through mucous membrane tissue and combinations thereof. The therapeutic agents can be administered by the same route or by different routes. [00128] Accordingly, combination therapies described herein can include the sequential administration of an antimicrobial agent, and/or an antispasmodic agent, and/or an LBP. In some embodiments, the sequence in which the therapeutic agents are administered is important for producing the desired combinatorial therapeutic effect. For example, in some dosing regimens an antimicrobial agent is typically administered for a period of time prior to the initial administration of the LBP. In some embodiments, the antimicrobial agent is administered to the subject about 30 minutes, about 1 hour, about 2 hours, about 4 hours, about 8 hours, about 12 hours, about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about 1 week, about 2 weeks or more before the initial administration of the LBP to the subject. In some embodiments, the LBP can be administered to the subject about 30 minutes, about 1 hour, about 2 hours, about 4 hours, about 8 hours, about 12 hours, about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about 1 week, about 2 weeks or more after the final administration of the antimicrobial agent to the subject. [00129] In some embodiments, the dosing regimen of the antimicrobial agent, and/or the antispasmodic agent, and/or the LBP to a subject may overlap for a period of time over the course of the subject’s treatment. For example, a subject may be first administered an antimicrobial agent and/or an antispasmodic agent for a period of time, followed by the administration of the antimicrobial agent and/or the antispasmodic agent and LBP for a period of time, and then only the LBP, or the antispasmodic and the LBP, is administered for a period of time until the end of the treatment. In some embodiments, the period of time where the administration of the antimicrobial agent and/or the antispasmodic agent and the LBP overlap during a combination therapy dosing regimen is about 1 hour, about 3 hours, about 6 hours, about 12 hours, about 1 day, about 2 days, about 3 days or more. In an exemplary embodiment, a subject can be simultaneously administered an antimicrobial agent and an LBP for about the final 24 hours or 48 hours of the antimicrobial agent dosing regimen and followed by only the administration of the LBP. [00130] In some embodiments, the combination therapy dosing regimen includes a period of time (i.e., a wash out period) between administration of the final dose of the antimicrobial agent and the initial administration of a dose of LBP. A wash out period can be used in order to allow colonization/recolonization of the LBP in the absence of the antibiotic, or a significant reduction in the amount of the antimicrobial agent remaining, in the urinary tract following antimicrobial agent treatment. In some embodiments, the wash out period is about 6 hours, about 12 hours, about 1 day, about 2 days, about 3 days or more. In other embodiments, a wash out period may not be required for the therapeutically effective treatment or prevention of urobiome dysbiosis in a subject. [00131] In certain embodiments, at least one of the two or more therapeutic agents of the combination therapy is administered via intravesicular administration. In some embodiments, an antimicrobial agent and/or an antispasmodic is administered systemically, and the LBP is administered intravesicularly. In particular embodiments, each of the antimicrobial agent, the antispasmodic agent, and the LBP are administered to a subject via intravesicular administration. In some embodiments, the antimicrobial agent and/or the antispasmodic agent can be administered both systemically and intravesicularly as needed over the course of a combination therapy described herein. [00132] Intravesicular administration typically involves delivery of a liquid therapeutic directly into the bladder. In some embodiments, intravesicular administration includes instillation of one or more therapeutic agents directly into the bladder via insertion of a urethral catheter. Instilled therapeutic agents described herein should be kept in the bladder for a period of time to ensure a therapeutically effective outcome. In some embodiments, the instillation should be kept in the bladder for a minimum of about 5 minutes, about 10 minutes, about 20 minutes, about 30 mins, about 45 minutes, about 60 minutes, and a maximum of about 90 minutes, about 120 mins, about 180 minutes or more. In exemplary embodiments, an antibiotic is instilled in the bladder of the subject and allowed to dwell about 1 hour. In some embodiments, for example in a subject undergoing intermittent catheterization, an LBP can be instilled in the bladder after urine drainage and remain in the bladder until the next catheterization and drainage. [00133] In some embodiments, the antimicrobial agent, and/or the antispasmodic agent, and/or the LBP of a combinatory therapy described herein are self-administered, or administered with caregiver assistance, and doesn’t require a medical professional’s presence. Standardized instructions on administration, including a tutorial on use and preparation of the antimicrobial agent, and/or the antispasmodic agent, and/or LBP and/or a step-by-step video can be provided to the subject in need thereof. In some embodiments, each of the antimicrobial agent, the antispasmodic agent, and LBP are self-administered via intravesicular administration. In an exemplary embodiment, both the antimicrobial agent and the LBP treatment are self-administered via intravesicular administration, e.g., bladder instillation. [00134] Therapeutic methods described herein can further include the administration of one or more additional therapeutic agents in combination with an antibiotic, and/or an antispasmodic agent, and/or an LBP to the subject. For instance, in some embodiments, a subject may be administered a therapeutically effective amount of one or more additional antimicrobial agent described above. The one or more additional antimicrobial agent(s) are not limited to administration via the same route as a first antimicrobial agent or LBP and may be administered by any suitable route, such as orally or systemically. For example, a second antimicrobial agent can be administered to a subject systemically following the intravesicular administration of a first antimicrobial agent and/or an antispasmodic agent, and/or an LBP, if need be, e.g., as determined necessary by a medical professional. [00135] In some embodiments, the one or more additional therapeutic agent administered to a subject in combination with an antimicrobial agent, and/or an antispasmodic agent, and/or an LBP for the treatment or prevention of urobiome dysbiosis described herein can include a prebiotic fiber. A prebiotic fiber, or simply a “prebiotic”, can be selected from the group consisting of inulin, fructo-oligosaccharides (FOS), galactooligosaccharides (GOS), and combinations thereof. In an exemplary embodiment, the prebiotic fiber is inulin. [00136] In some embodiments, one of several weak organic acids (WOAs) can be administered in addition to an antimicrobial agent and/or an antispasmodic agent, and/or LBP combination therapy in order to inhibit the adhesion of uropathogenic bacteria in the lower urinary tract and promote growth of beneficial probiotic bacteria species. WOAs for use in a method described herein can include citric acid, acetic acid, quinic acid, and malic acid. In particular embodiments, the WOA is citric acid or acetic acid. In an exemplary embodiment, citric acid or acetic acid can be included in a pharmaceutically acceptable carrier used to formulate an LBP for intravesical administration to the subject. [00137] In other embodiments, a steroid can be administered to a subject in addition to an antimicrobial agent, and/or antispasmodic agent, and/or LBP combination therapy described herein. In certain embodiments, the steroid is a corticosteroid. Exemplary corticosteroids can include, but are not limited to, alclometasone, amcinonide, beclometasone, betamethasone, budesonide, ciclesonide, clobetasol, clobetasone, clocortolone, cloprednol, cortivazol, deflazacort, deoxycorticosterone, desonide desoximetasone, dexamethasone, diflorasone, diflucortolone, difluprednate, fluclorolone, fludrocortisone, fludroxycortide, flumetasone, flunisolide, fluocinolone acetonide, fluocinonide, fluocortin, fluocortolone, fluorometholone, fluperolone, fluticasone, fluticasone propionate, fluprednidene, formocortal, halcinonide, halometasone, hydrocortisone aceponate, hydrocortisone buteprate, hydrocortisone butyrate, loteprednol, medrysone, meprednisone, methylprednisolone, methylprednisolone aceponate, mometasone furoate, paramethasone, prednicarbate, prednisone, prednisolone, prednylidene, rimexolone, tixocortol, triamcinolone, ulobetasol, and combinations thereof, [00138] In some embodiments, an NSAID can be administered to a subject in addition to an antimicrobial agent, and/or an antispasmodic agent, and/or LBP combination therapy described herein. NSAIDs can refer to any of variety of drugs generally classified as non- steroidal anti-inflammatory drugs including, but not limited to, ibuprofen, flurbiprofen, diclofenac, salicylates (e.g. aspirin), COX2 inhibitors (e.g., celecoxib), indomethacin, piroxicam, naproxen, acetaminophen, and combinations thereof. [00139] Subjects treated in accordance with a method described herein can include any subject having, or at risk of having or developing, urobiome dysbiosis. For example, a subject may not have urobiome dysbiosis when a treatment begins. In some embodiments, urobiome dysbiosis in a subject may be characterized by the presence, and/or the overabundance, of extended-spectrum beta-lactamase (ESBL) producing pathogens in the lower urinary tract of a subject. ESBLs are enzymes or chemicals produced by certain pathogens, such as bacteria and typically make bacterial infections harder to treat with antibiotics. Bacteria that produce ESBLs include, but are not limited to, Escherichia coli and Klebsiella pneumoniae. [00140] In some embodiments, the subject in need of a combination therapy described herein can have a spinal cord injury or disorder (SCI/D). In certain embodiments, the subject has had a SCI/D for at least about 6 months prior to the start of a combination therapy described herein. [00141] In some embodiments, subjects treated in accordance with a method described herein can include a subject that manages their bladder through, at least in part, the use of catheterization. For example, a subject may use intermittent catheterization (IC) or indwelling catheterization (IDC) for bladder management. In some embodiments, a subject managing their bladder using catheterization may be at risk of a Catheter-Associated Urinary Tract Infection (CAUTI). CAUTI’s occur when bacteria or yeast travel along the catheter and cause an infection in a subject’s bladder or kidney. The most important risk factor for developing a catheter-associated UTI (CAUTI) is prolonged use of the urinary catheter. [00142] In some embodiments, a subject in need of a combination therapy described herein can include a subject having a neurogenic lower urinary tract dysfunction (NLUTD), previously referred to as a Neurogenic Bladder (NB). An NLUTD-subject can utilize a urinary catheter which may be used (a) on an intermittent basis for just long enough to empty the bladder, (b) short term (hours or days, e.g. intra- and immediately post-operation), (c) longer term (few days to weeks, e.g. post-operation), or (d) continuous or chronic long term (30 days or more, e.g. spinal cord injuries or disorders (SCI/Ds) and in Long Term Care Facilities (LTCFs)). An indwelling catheter that is left in place for a period of time is in general attached to a sterile container to collect the urine. The most commonly used Foley indwelling catheter is a soft silicone or latex tube that is inserted into the bladder through the urethra to drain the urine and is retained by a small balloon inflated with air or liquid. Urinary catheters come in a large variety of sizes, materials (latex, silicone, uncoated or coated with other materials such as silicone, hydrogel, antibacterial agents, etc.), and types (Foley catheter, straight catheter, Coude-tip catheter, etc.). Catheters are generally placed into the bladder through the urethra, but in some cases, an NLUTD-subject of the present invention may have a suprapubic indwelling catheter that is placed directly into the bladder through a surgically prepared opening (stoma) in the abdomen above the pubic bone. Catheters can be replaced at a variety of frequencies but are generally replaced about once a month. [00143] While subjects with NLUTD can result from any trauma or disease of the brain or spinal cord, people with spinal cord injury or disorder (SCI/D), multiple sclerosis (MS), and spina bifida (SB) are heavily affected. Therefore, in specific embodiments, subjects treated in accordance with a method described herein can include individuals with NLUTD due to SCI/D, MS or SB. In particular embodiments, a subject treated can include an individual that is 1-year post SCI/D or a subject at least 6 years old with SB. [00144] In some embodiments, a subject (e.g., a NLUTD-subject) administered a combination therapy as described herein has asymptomatic bacteriuria (ABU). ABU is a colonization of a portion of the urinary tract by bacteria that does not display the symptoms typically seen for a urinary tract infection. The urine samples obtained from a subject with asymptomatic bacteriuria may look infected (as evaluated by dipstick, for example) and will result in bacterial growth if cultured. However, it is difficult to determine if this represents an early infection that can be treated briefly to avoid complications, or just bladder colonization with non-pathogenic bacteria that does not represent a problem and will likely not be cleared by treatment with antibiotics. Not all asymptomatic infections represent chronic infections. Some types of subjects will be asymptomatic as a result of a lack of inflammatory response due to immunosuppression (e.g., transplant patients) or lack of sensation of symptoms as a result of, for example, having spinal cord injuries or congenital spinal/neural tube defects. [00145] In some embodiments, a subject, such as an NLUTD-subject, in need of a combination therapy described herein may suffer from, or be at an increased risk of, a urinary tract infection (UTI) or is more susceptible to a severe urinary tract infection. A more severe form of UTI can be a UTI exhibiting one or more urinary symptoms that are problematic and/or painful to a subject. For example, a subject may not have a currently diagnosed UTI but may be considered at an increased risk of a UTI. An increased risk refers to a higher likelihood or percent possibility of having a urinary tract infection in comparison with a control subject. In some embodiments, a control subject can include an NLUTD subject who is not at an increased risk of UTI (e.g., an NLUTD-subject with stable asymptomatic bacteriuria) or a healthy non- NLUTD subject. [00146] A subject having a UTI may have either an uncomplicated UTI or a complicated UTI. UTIs can be differentiated between simple and complicated UTIs by a medical practitioner based on risk factors, clinical presentation, and potential complications. A simple UTI can include an infection of the urinary tract due to appropriate susceptible bacteria, typically an infection in an afebrile non-pregnant immune-competent female subject. UTIs can be complicated by several risk factors leading to treatment failure, repeat infections, or significant morbidity and mortality with a poor outcome. A complicated UTI can include any UTI other than a simple UTI. Therefore, UTIs in immunocompromised subjects, males, pregnant patients, and those associated with fevers, stones, sepsis, urinary obstruction, catheters, or involving the kidneys can be considered complicated UTIs. In some embodiments, a subject may suffer from recurrent UTIs. In some cases, a recurrent UTI can be considered a simple UTI. For example, a recurrent UTI can be considered simple provided there is a prompt response to first-line antibiotics without any long-term sequela. On the other hand, recurrent UTI despite adequate treatment can be considered a complicated UTI. [00147] A UTI is typically a bacterial infection. The bacteria can be gram-negative bacteria, or the bacterial can be gram-positive bacteria. For example, the bacteria can be one or more of E. coli, Pseudomonas, Enterococcus, Enterobacter, Klebsiella, or Proteus mirabilis. The majority (80-85%) of bacterial urinary tract infections are caused by E. coli. However, a urinary tract infection can also occur as a result of infection by pathogens other than bacteria. For example, urinary tract infections can also be caused by viruses and fungus. Examples of urinary viral infections include those by BK virus, cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Fungal infection is commonly caused by infection by fungi of the genus Candida. [00148] In some embodiments, UTI can also be diagnosed in a subject using laboratory diagnostic methods that may include culturing urine samples obtained from the subject. In some embodiments, any well-known UTI screening methods can be used in addition to the methods described herein to confirm or aid in diagnosing UTI infection in a subject. Additional non-limiting screening methods for UTI can include the use of urine culture, blood culture, a complete blood count (CBC), ultrasound, intravenous pyelogram (IVP), and cystoscopy. [00149] In other embodiments, a subject treated in accordance with a method described herein may not have one or more symptoms of a UTI. For example, a subject, in particular a subject utilizing intermittent catheterization, may not have an actionable or bladder symptom of a UTI. Actionable symptoms of a UTI can include feeling feverish, increased tone/spasticity of the bladder, bladder spasm frequency/discomfort, abdominal/suprapubic pain, dizziness, headache, autonomic dysreflexia related to spinal cord injury, and an increase in irritability, fatigue, lethargy, or weakness. Bladder symptoms of a UTI can include a change in the quality of pain when passing urine and/or catheterization, incontinence/urine leakage, urinary urgency, increase in catheterization, decreased urine volume during catheterization, and blood in urine. [00150] In some embodiments, a subject in need of urobiome dysbiosis treatment or prevention can be identified using one or more urine tests on urine obtained from the subject. In some embodiments, the one or more urine tests are selected from urinalysis (UA), urine culture, and susceptibility tests. A urinalysis can involve performing several tests on urine. These tests include an examination of the urine under a microscope and chemical tests that check the urine for various substances and/or microorganisms. A urine dipstick is one type of chemical test that may be performed during a urinalysis. A urine culture test allows bacteria from the urine of a subject to be grown in a controlled laboratory environment and can be used to identify the specific species of bacteria in the subject’s urobiome. Susceptibility testing may be performed once bacteria have grown in the urine culture. Those bacteria are exposed to various antibiotics to identify the most effective one to use in treating a subject identified as in need of urobiome dysbiosis treatment. [00151] A subject in need of urobiome dysbiosis combination therapy as described herein, may also be identified by measuring the amount of urobiome probiotic species and/or uropathogenic bacterial species colonization in a sample obtained from a subject, and comparing the amount of urobiome probiotic bacterial colonization and/or uropathogenic bacterial species in the sample to a threshold amount, and identifying a subject having an insufficient amount of probiotic bacterial colonization and/or an excessive amount of uropathogenic bacterial in the urobiome. In other embodiments, a subject in need of a combination therapy as described herein can be identified by determining the abundance ratio of urobiome uropathogenic bacteria to probiotic bacteria in the subject’s urinary tract, wherein the identified ratio compared to a control value is indicative of the subject having, or at risk of, urobiome dysbiosis. [00152] Diagnosis of the subject’s urobiome dysbiosis can also include assaying the subject’s urine to determine the presence or absence of one or more particular bacterial species found to be associated with a greater risk of severe urogenital infection. Therefore, in some embodiments, the presence of emerging bacterial species in the urobiome of a subject as determined in a subject’s urine sample can be included in a determination to initiate a combination of an antimicrobial agent, and/or an antispasmodic agent, and/or an LBP treatment. In certain embodiments, the presence of L. iners and/or a Burkholderia species (e.g., Burkholderia cepacian) and/or the absence of L. crispatus in a subject’s urine sample can be indicative of urobiome dysbiosis that places the subject at a greater risk for disease and therefore can trigger combinatory antimicrobial agent, and/or antispasmodic agent, and/or LBP treatment as described herein. [00153] In order to determine the bacterial species and/or the abundance thereof in a subject, a sample including lower urinary system bacteria should be obtained. As the invention is directed towards treating and/or preventing urobiome dysbiosis in a subject, the sample should be one including bacterial species associated with urobiome dysbiosis. An example of a suitable sample includes urine samples. A variety of methods are known to those skilled in the art for obtaining a urine sample. Urine can be collected from an individual by suprapubic aspiration. This method represents the ideal method for obtaining a urine sample. However, it is not performed routinely in clinical practice in which urine ^^^^^^^^^^^^%^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^is setting, some degree of artifactual contamination with normal urethral organisms occurs. [00154] A standard method for obtaining a urine sample can be referred to as the clean- catch sample method. To obtain an untainted urine sample, doctors usually request a so- called midstream, or clean-catch, urine sample. To provide this, the subject washes the area from which urine will issue, urinates a small amount into the toilet for a few seconds and then stops, position the container to catch the middle portion of the stream, urinates until the collection cup is halfway full (about 2 ounces), and then removes the cup. The collection cup should then be sealed with a cap and given to the doctor or sent to the laboratory for analysis. [00155] Alternately, urine can be collected with a catheter. Some patients (e.g., small children, elderly people, or hospitalized patients) cannot provide a urine sample. In such cases, a catheter may be inserted into the bladder to collect urine. This is the best method for providing a contaminant-free sample but has the disadvantage of possibly introducing or spreading infection and discomfort to the subject. [00156] The urine sample may be pretreated as necessary by dilution in an appropriate buffer solution and concentrated or fractionated by any number of methods including but not limited to ultracentrifugation, fractionation by fast performance liquid chromatography (FPLC), or precipitation. Any of a number of standard aqueous buffer solutions at physiological pH, such as phosphate, Tris, or the like, can be used. [00157] Once a sample has been obtained, an analytic device is used to measure the levels of bacterial species. The analytic device can be either a portable or a stationary device. In addition to including equipment used for detecting the bacterial species, the analytic device can also include additional equipment to provide physical separation of analytes prior to analysis. For example, if the analyte detector is an immunoassay, it may also include an ion exchanger column chromatography to purify the proteins from urine before the specific detection of bacterial species by immunoassay. Methods for detecting bacterial species are known to those skilled in the art. For example, urine samples can be assayed using urinalysis, and/or urine culture. An alternate method for determining the predominant bacterial species is by using a polymerase chain reaction (PCR)-based assay, such as multiplex PCR. [00158] In some embodiments, a bacterial species of interest that is shown to be associated with urobiome dysbiosis in subjects is one that is not routinely cultured. Bacterial species that are not routinely cultured can be assayed using 16S ribosomal sequencing. Unlike capillary sequencing or PCR-based approaches, next-generation-based 16S sequencing (NGS) is a culture-free method that enables analysis of the entire microbial community within a sample. With the ability to combine many samples in a sequencing run, operators can use NGS-based 16S rRNA sequencing as a cost-effective technique to identify strains that may not be found using other methods. In some embodiments, shotgun sequencing can be used to detect, profile, and/or functionally analyze bacterial species in a urine sample obtained from a subject. Shotgun sequencing or metagenomics is a deep sequencing approach in which all the DNA in a sample is fragmented and sequenced, then reassembled into genomes that represent the different organisms present i^^^^^^^^^^^^^^^^ urine, this might include DNA from bacteria, viruses, fungi, as well as the human host. [00159] Once the levels of bacterial species have been determined, they can be displayed in a variety of ways. For example, the levels of specific bacterial species can be displayed graphically on a display as numeric values or proportional bars (i.e., a bar graph) or any other display method known to those skilled in the art. The graphic display can provide a visual representation of the amounts of the various bacterial species in the samples being evaluated. In addition, in some embodiments, the analytic device can also be configured to display a comparison of the levels of bacterial species in the subject’s urine to a control value based on levels of bacterial species in a comparable urine sample, urine samples from a reference cohort, or a standard numerical reference. [00160] Embodiments described herein also relate to a system for selecting a treatment for urobiome dysbiosis in a subject. The system includes screening the subject for urobiome dysbiosis, or the risk of developing urobiome dysbiosis. The system also includes the step of selecting a proper treatment if the subject has urobiome dysbiosis or the subject’s risk of developing urobiome dysbiosis exceeds a threshold. The proper treatment can include a combination therapy of an antimicrobial agent, and/or an antispasmodic agent, and/or an LBP described herein. [00161] In some embodiments, the step of screening the subject for urobiome dysbiosis, or for the risk of developing urobiome dysbiosis, can include any method described herein, such as performing a urine analysis assay on a urine sample obtained from the subject. A urine analysis assay can be used to determine the abundance of one or more uropathogenic bacterial species in the sample. Alternatively, or in addition, a urine analysis assay can be used to determine the abundance of one or more probiotic bacterial species in the sample. The abundance of the uropathogenic bacterial species and/or the abundance of the probiotic bacterial species can be compared to a control/threshold amount in order to select a proper treatment. Urine analysis can be performed routinely as necessary, for example as determined necessary by a medical practitioner. In some embodiments, urine analysis can be performed on a urine sample obtained from a subject about every 2 to 3 days. [00162] In addition to the methods described above, the step of screening the subject for urobiome dysbiosis, or the subject’s risk of developing urobiome dysbiosis, may also include providing a questionnaire to the subject. The subject completes the questionnaire and, based on the data from the subject’s answers, the presence of urobiome dysbiosis or the subject’s risk of developing urobiome dysbiosis can then be determined. In accordance with a system described herein, the questionnaire can include a urinary symptom questionnaire or similar survey instrument. A questionnaire for use in a system described herein can be a tool for an individual, to monitor their need to initiate or stop management of urobiome dysbiosis or symptoms thereof through the use of combination therapy and when to abandon an antimicrobial agent, and/or antispasmodic, and/or LBP combination treatment (e.g., through self-management) in favor of seeking further medical assistance (e.g., for a febrile UTI). [00163] In some embodiments, the urinary symptom questionnaire is a subjective urinary symptom questionnaire. The screening step can include having the subject answer questions from a urobiome dysbiosis screening questionnaire and scoring the questionnaire. Typically, the questionnaire is performed in private by the subject or a caregiver and the results kept confidential. In some embodiments, systems described herein are performed using a computer process. For example, one or more of the screening, diagnosing, treatment selection, administration steps can be utilized as part of an algorithm implemented in a computer program. The computer program can be run by a health care provider or the subject themselves. [00164] A questionnaire for use in a method of the present invention can include questions related to urinary symptoms, such as those focusing on urinary signs and lower urinary tract symptoms (LUTS). Questions may refer to the frequency, severity and the impact of urinary symptoms on an individual. A questionnaire for use in a method described herein can be based on patient experiences related to the onset and progression of symptoms that occurred in a previously diagnosed urobiome dysbiosis. In some embodiments, additional questions may be added in subsequent questionnaires following administration of a baseline questionnaire. [00165] A questionnaire can include questions in terms of the presence, frequency, severity, and the impact of urinary symptoms on individuals, such as those with SCI/D and/or NLUTD. In some embodiments, the questionnaire can have 200, 150, 100, 50, 30, 20, or fewer items identified as relevant to urobiome dysbiosis symptoms in a subject. In some embodiments, the questionnaire can have 15 or fewer items. In some embodiments, subjects are instructed to complete the questionnaire every week, every two weeks, or every three weeks. In some embodiments, subjects are instructed to complete the questionnaire once a week. In some embodiments, subjects are instructed to complete the questionnaire whenever urinary symptoms occur to determine whether to initiate an antimicrobial agent, and/or antispasmodic agent, and/or LBP combinatory treatment. [00166] Examples of urinary symptoms to be surveyed in a questionnaire can include, but are not limited to, dark color urine, blood in urine, pink urine, cloudy and/or milky appearing urine, sediment in urine, white discharge, malodorous urine (bad-smelling, strong, foul, or pungent urine), an increase in bladder spasm, urgency or frequency, incontinence, leakage, ineffective catheterization, pain in abdomen, pain in lower back, pain in legs, pain in penile or urethral region, pain during bladder spasm, burning or irritation on catheterization or passing urine, pain based on body position (sitting versus standing or lying down), feeling feverish, fatigue, lethargy, altered sleep patterns, weakness, irritability, general sense of not feeling well, muscle aches, headaches, dizziness, increased lower body tone, rigor or spasticity, abdominal bloating, nausea, stomach pain, loss of appetite, and changes in bowel patterns. [00167] Scoring of the questionnaire can include providing a cumulative score of the number of items (urinary symptoms) endorsed by the subject or subject caregiver. Scoring can also be related to the frequency, severity, and the impact of urinary symptoms on a subject. For example, a subject indicating that they are experiencing greater frequency of a particular urinary symptom may generate a greater relative score. [00168] Based on the answers provided in a questionnaire and/or a generated score, a proper treatment for the subject can be selected and/or initiated. For example, a combination antimicrobial agent, and/or antispasmodic agent, and/or LBP treatment as described herein can be initiated when a generated score or set of responses reach a particular threshold of urobiome dysbiosis risk. The threshold of urobiome dysbiosis can be a particular number, amount, degree, and/or a combination of urinary symptoms identified during the screening step (e.g., through the use of a questionnaire) triggering or guiding the selection of the administration of a proper combination antimicrobial agent, and/or antispasmodic agent, and/or LBP treatment to the subject but that does not require other immediate relative medical attention. The threshold of urobiome dysbiosis risk can be a predetermined number, amount, degree, and/or a combination of urinary symptoms wherein any value greater than the predetermined number, amount, degree, and/or a combination of urinary symptoms triggers or guides the selection of the administration of a proper antimicrobial agent, and/or antispasmodic agent, and/or LBP combination treatment to the subject. In some embodiments, the threshold can include a cumulative point total of endorsed items from a questionnaire that is greater than or equal to a point total predetermined by a health care professional that indicates that a subject can benefit from antimicrobial agent, and/or antispasmodic agent, and/or LBP combinatory treatment. [00169] Urinary symptoms identified in a questionnaire and meeting or exceeding a threshold and thus triggering a combination of an antimicrobial agent, and/or antispasmodic agent, and/or LBP treatment in a subject can be one or more problematic urinary symptoms not commonly found in a control population. In some embodiments, a control population can include individuals with SCI/D and/or NLUTD having asymptomatic bacteriuria (ABU) that does not proceed to severe urogenital infection. In other embodiments, a control population can include healthy individuals without SCI/D and/or NLUTD. The threshold of urobiome dysbiosis risk can be a predetermined number, amount, degree, and/or a combination of urinary symptoms wherein any value greater than the number, amount, degree, and/or a combination of urinary symptoms derived from a control population, triggers or guides the selection of the administration of a proper antimicrobial agent, and/or antispasmodic agent, and/or LBP treatment to the subject. [00170] Subjects diagnosed or identified as having urobiome dysbiosis in the screening step as described herein, (e.g., those subjects susceptible to urobiome dysbiosis-related NLUTD and/or UTI as determined using a questionnaire and/or assays described above) can be treated with a proper treatment. A proper urobiome dysbiosis treatment selected for a given subject can include the intravesicular administration of the combination of an antimicrobial agent, and/or antispasmodic agent, and/or an LBP, described above. [00171] In some embodiments, no treatment is required or triggered by scoring or reviewing the questionnaire and the subject can continue to be screened using a urine assay and/or questionnaire as necessary. In other embodiments, one or more assay results or answers to the questionnaire (e.g., that they have a fever greater than 100.4^oF) can indicate that subject requires medical assistance including, but not limited to, systemic antibiotic treatment. Similarly, if urinary symptoms persist or worsen medical assistance outside of intravesical administration of an antimicrobial agent, and/or antispasmodic agent, and/or an LBP combinatory treatment can be sought by the subject. [00172] In some embodiments, the questionnaire is a treatment decision tree embedded in a patient questionnaire. The decision tree can include decision points that guide the selection of proper treatment based on how individuals rate the frequency, severity, or impact of their urinary symptoms, plus any clinical indicators of progression of urobiome dysbiosis to a point where the individual’s risk is inconsistent with continued intravesical antimicrobial agent, and/or antispasmodic agent, and/or LBP combinatory treatment and requires medical attention (e.g., where the subject indicates that they have a fever greater than 100.4^oF). [00173] Systems and methods described herein can further include selecting and/or performing continued urobiome dysbiosis monitoring on the subject if the subject. For example, continued urobiome monitoring using a urine assay and/or questionnaire can occur if a subject is determined to be at continued risk of urobiome dysbiosis and/or following a combination therapy described herein. [00174] Formulations of therapeutic agents described herein may contain one or more excipients such as carriers, solvents, stabilizers, adjuvants, diluents, etc. Pharmaceutically acceptable excipients are determined in part by the particular composition being administered, as well as by the particular method used to administer the composition. Accordingly, there exists a wide variety of suitable formulations of pharmaceutical compositions (see, e.g., Remington’s Pharmaceutical Sciences). The pharmaceutical compositions should generally be formulated to achieve a physiologically compatible pH and may range from a pH of about 3 to a pH of about 11, preferably about pH 3 to about pH 7, depending on the formulation and route of administration. In alternative embodiments, it may be preferred that the pH is adjusted to a range from about pH 5.0 to about pH 8. More particularly, the pharmaceutical compositions may comprise a therapeutically or prophylactically effective amount of at least one compound as described herein, together with one or more pharmaceutically acceptable excipients. Optionally, the pharmaceutical compositions may comprise a combination of the compounds described herein or may include one or more additional active therapeutic ingredients, agents, or adjuvants useful in the treatment or prevention of urobiome dysbiosis. [00175] Formulations for administering a therapeutic agent in a method described herein typically include an adequately buffered solution. An adequately buffered solution should be considered to reduce drug precipitation. Formulations may include for example, sterile water, instillation buffers such as Tris buffer, phosphate-buffered saline (PBS) and saline. An antimicrobial agent, and/or antispasmodic agent, and/or LBP administered in accordance with a therapeutic method described herein, may be formulated for administration by a variety of routes. In particular embodiments, the antimicrobial agent, and/or antispasmodic agent, and/or LBP are formulated in a manner suitable for intravesicular administration. In some embodiment, formulations for intravesicular administration can include an adequately buffered normal saline solution. In some embodiments, formulations for intravesicular administration of one or more therapeutic agents described herein can include a citric acid buffered normal saline solution. [00176] In some embodiments, one or more the therapeutic agents described herein can be formulated into a unit dosage form. Non-limiting examples of dosage forms of into which the therapeutic agents and any additional material such as a carrier can be incorporated include capsule, chewable tablet, swallowable tablet/pill, buccal tablet, coated tablet, troche, powder, lozenge, soft chew, solution, suspension, spray, extract, tincture, oil, decoction, infusion, syrup, elixir, wafer, food product, and combinations thereof. The dosage forms can comprise ingestible carriers, non-limiting examples of which include solid or liquid filler diluents, encapsulating substances, and mixtures and ^^^^^^^^^^^^^^^^^^^^^^^^%^^^^^^^^^^^^^^^ ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^%^^^^^^^^^^^^^^%^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^^%^^^^^^^^^^^^^^^^^^^%^^^^^^^^^^^^^^^^^^^^^^^%^^^^^^%^^^^^^^^^^^^^^^%^^-^^^^^^^^^^^^^^^^^^^^^ ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^%^^%^^^^^^^^^^^^^^^^^^^^^^^^^%^^%^^^^^^^^^^^^^^%^ ^%^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ [00177] The therapeutically effective amount of an LBP, e.g., a probiotic, and/or antimicrobial agent, and/or antispasmodic agent treatment administered to a subject as described herein can include an amount of antimicrobial agent, and/or antispasmodic agent, and/or LBP that is effective to achieve alleviation of symptoms of the health problems, conditions, and/or diseases managed by the methods and of the present invention. The amount of the respective LBP, and/or antimicrobial agent, and/or antispasmodic agent administered will, of course, be dependent on the subject and disease/disorder state being treated, the severity of the affliction (e.g., urobiome dysbiosis), the particular combination of agents included in a combination therapy as described herein, the manner and schedule of administration, and the judgment of the prescribing physician. [00178] The therapeutically effective amount of a combination therapy described herein can be measured and/or defined in numerous ways. In some embodiments, the therapeutic amount of an antimicrobial agent, and/or an antispasmodic agent, and LBP combination therapy described herein can be the amount required to reduce the abundance of native and/or uropathogenic bacterial species in the urinary tract and to allow colonization or recolonization of the LBP, e.g., a beneficial probiotic bacterial species, in the urinary tract of the subject. [00179] In some embodiments, the therapeutically effective amount of a combination therapy described herein can include the amount effective to prevent, inhibit and/or reduce the frequency, degree of severity and/or impact one or more uropathogenic related LUTS or a UTI in the subject. Exemplary uropathogenic bacterial species responsible, at least in part, for LUTS or UTI in a subject can include uropathogenic Escherichia coli (UPEC), as well as Shigella and Aerococcus, Klebsiella, Proteus, Pluralibacter, and Enterococcus uropathogenic bacterial species. [00180] In some embodiments, the therapeutically effective amount of an LBP is the amount required to successfully colonize/recolonize the lower urinary tract with the LBP, e.g., a probiotic, following antimicrobial agent (e.g., antibiotic treatment) and/or antispasmodic agent treatment. In some embodiments, successful colonization/recolonization with an LBP can include at least a 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or more increase in the abundance of the LBP in the urobiome compared to a control amount. A control amount can include a baseline abundance of an LBP measured in the subject’s urobiome prior to the administration of the combination of therapeutic agents. In some embodiments, the baseline measurement for a particular LBP can be zero and in which case the increase in the abundance of the LBP will be absolute. [00181] A therapeutically effective amount of a combination therapy described herein can include the amount required for successful (e.g., robust) colonization or recolonization of a probiotic bacterial species in the urinary tract of the subject. In some embodiments, successful colonization of the urobiome can be identified in a subject by measuring the amount of a therapeutic probiotic in a sample obtained from the bladder of a subject following treatment. In some embodiments, the successful colonization/recolonization is the presence of a threshold value of the measured probiotic species and/or a threshold value of measured uropathogen in the urobiome of the subject. The threshold value(s) may be identified using data taken from subjects previously treated using a combination therapy described herein, wherein the threshold value(s) correlated to a therapeutically effective treatment. For example, successful colonization, or recolonization, of a probiotic bacterial species in the urinary tract of the subject can be defined as the urobiome of the urinary tract having a measured probiotic bacterial density of about 10³ to about 10⁴ CFU/m. [00182] The effectiveness of a particular combination therapy described herein can be determined by measuring the amount of LBP colonization in the urobiome of a subject following administration of the combination therapy and comparing an increase in the amount of LBP colonization in the sample to a threshold amount or a ratio of uropathogen to LBP, (e.g., a probiotic bacterial species), and identifying a subject having an insufficient amount of probiotic bacterial colonization. In an exemplary embodiment the therapeutically effective amount is the amount required to improve the ratio of uropathogen(s) to a Lactobacillaceae probiotic (i.e., U/L ratio) by about 25% in the urobiome of a subject compared to a control. The control can include a baseline ratio of uropathogen to a particular probiotic species measured prior to the administration of either therapeutic agent. [00183] Individual therapeutic agents described herein can be administered in accordance with the methods and systems at any frequency as a single dose or multiple doses, e.g., one, two, three, four, five, or more times hourly, daily, weekly, monthly, or annually or between about 1 to 10 days, weeks, months, or for as long as appropriate. Exemplary frequencies are typically from 1-7 times, 1-4 times, 1-3 times, 2-times or once, daily, weekly or monthly. Timing of administration can be dictated by the urobiome dysbiosis, symptoms, pathology or adverse side effect(s) to be treated. For example, a therapeutically effective amount of a therapeutic agent can be administered to the subject substantially contemporaneously with, or within about 1 minute to about 60 minutes, hours, days, or even weeks from the onset of a symptom related to urobiome dysbiosis in a subject. In other embodiments, a therapeutically effective amount can be administered to the subject substantially contemporaneously with, or within about 1-60 minutes, hours, days, or weeks or of the completion of a urinalysis assay and/or questionnaire indicating urobiome dysbiosis or the risk of urobiome dysbiosis in the subject. [00184] In an exemplary embodiment of the combination therapy dosing regimen, the antimicrobial agent of the combination therapy is administered to the subject twice daily for 5 days (10 total doses). By way of example, the first intravesicular administration of an antimicrobial agent is via bladder instillation and occurs following a morning catheterization. Then, about 12 hours after the final dose of the antimicrobial agent the first dose of an LBP is administered and then subsequently every 12 hours until the dosing regimen of the LBP is completed. For example, the dosing regimen of the LBP may end after a total of 2 to 4 doses. [00185] Doses may vary depending upon whether the treatment is therapeutic or prophylactic, the onset, progression, severity, frequency, duration, probability of or susceptibility of a particular symptom, the type pathogenesis to which treatment is directed, clinical endpoint desired, previous, simultaneous or subsequent treatments, general health, age, gender or race of the subject, bioavailability, potential adverse systemic, regional or local side effects, the presence of other disorders or diseases in the subject, and other factors that will be appreciated by the skilled artisan (e.g., medical or familial history). Dose amount, frequency or duration may be increased or reduced, as indicated by the clinical outcome desired, status of the infection, symptom or pathology, any adverse side effects of the treatment or therapy. The skilled artisan will appreciate the factors that may influence the dosage, frequency and timing required to provide an amount sufficient or effective for providing a prophylactic or therapeutic effect or benefit. The exact dosage will be determined by the practitioner, in light of factors related to the subject that requires treatment. Dosage and administration are adjusted to provide sufficient levels of the active therapeutic agents or to maintain the desired effect. It will be appreciated that treatment as described herein includes preventing urobiome dysbiosis or related disease or disorder, ameliorating symptoms, slowing disease progression, reversing damage, or curing a disease. [00186] The dosage may range broadly, depending upon the desired effects and the therapeutic indication. Alternatively, dosages may be based and calculated upon the surface area of the patient, as understood by those of skill in the art. Although the exact dosage will be determined on a drug-by-drug basis, in most cases, some generalizations regarding the dosage can be made. The daily dosage regimen for an adult human patient may be, for example, a dose of between about 0.01 mg and about 3000 mg of the active ingredient, preferably between 1 mg and 700 mg, e.g., 5 to 200 mg. The dosage may preferably depend upon the body weight of the patient. For example, the dosage may be between 0.01 mg/kg and 3000 mg/kg of the active ingredient, preferably between 1 mg/kg and 1000 mg/kg, e.g., 5 to 200 mg/kg or 10 to 100 mg/kg. The dosage may be a single one or a series of two or more given in the course of one or more days, as is needed by the subject. In some embodiments, the compounds will be administered for a period of continuous therapy, for example for a week or more, or for months or years. In some embodiments, a human subject can be administered an antibiotic at doses of about 10 mg to about 100 mg per instillation. [00187] In some embodiments, a LBP, (e.g., a probiotic bacterial species) can be administered at a concentration of from about 1 x 10³ to about 1 x 10¹⁴ colony forming units (cfu) of probiotic, alternatively from about 1 x 10 to about 1 x 10¹⁴ cfu of probiotic, alternatively from about 1 x 10⁷ to about 1 x 10¹⁴ cfu of probiotic, alternatively from about 1 x 10⁹ to about 1 x 10¹² cfu of probiotic, and alternatively from about 1 x 10¹⁰ to about 1 x 10¹² cfu of probiotic, and alternatively from about 1 x 10¹¹ to about 1 x 10¹²cfu of probiotic, per dose or per day. [00188] In particular embodiments, the LBP probiotic bacterial species is Lacticaseibacillus rhamnosus GG and the antimicrobial agent is the antibiotic gentamicin. By way of non-limiting example, the administration of a probiotic treatment to a subject in need thereof can include intravesicular Lacticaseibacillus instillation where a subject is instructed to mix the contents of a Lacticaseibacillus rhamnosus GG (ATCC 53103) capsule including 40mg (10 billion active probiotic cultures) of Lacticaseibacillus GG plus Inulin (a prebiotic) into 30 cc sterile normal 0.9% saline. After mixing, the subject draws up the 30cc liquid Lacticaseibacillus mixture into a 60cc catheter tip syringe, instills the mixture via the urinary catheter, and then clamps the catheter for about 30 minutes. [00189] By way of another non-limiting example, the administration of an antibiotic to a subject in need thereof can include intravesicular gentamicin instillation where a subject is instructed to mix 480 mg gentamicin in 1 L normal saline. After mixing, the subject draws up the 60cc (28.8 mg) liquid solution into a 60cc catheter tip syringe and instills the mixture ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^%^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^*^^^^^^^ the solution is left indwelling until the next catheterization. [00190] Additional embodiments relate to a therapeutic kit to provide prevention and/or treatment of urobiome dysbiosis in a subject in need thereof. The kit includes an effective dosage of an antimicrobial agent, and/or an antispasmodic agent, and/or an LBP, and equipment necessary to perform self-administered antimicrobial agent, and/or antispasmodic agent, and/or LBP therapy. A kit may also include information and equipment necessary to prepare and/or formulate one or more effective doses of the combination of therapeutic agents for self-administration, e.g., via intravesicular administration. [00191] A kit typically includes packaging assembly having a container suitable for accommodating items in the kit. The kit may further include a urine diagnostic test for screening a subject for urobiome dysbiosis or the risk of developing urobiome dysbiosis, and the equipment necessary to perform a self-administered urine diagnostic test, such as a plurality of urine collection containers. The kit can also include a questionnaire as described above and can be used to determine if a user is suitable for antimicrobial agent, and/or antispasmodic agent, and/or LBP combination therapy included in the kit. [00192] A kit in accordance with embodiments described herein may also include information relating to the antimicrobial agent, and/or antispasmodic agent, and/or LBP and instructions on how to select and self-administer the antimicrobial agent, and/or antispasmodic agent, and/or LBP. In particular embodiment, the kit includes one or more doses of gentamicin and Lacticaseibacillus rhamnosus GG probiotic treatment. In some embodiments, the kit includes one or more doses of oxybutynin (Ditropan). [00193] A urine diagnostic test can include a single parameter test or a multiparameter urine diagnostic test. For example, the urine diagnostic test can include a multiparameter urine test strip. In some embodiments, the multiparameter urine test strip can test for one or more of leukocytes, nitrite, protein, blood, pH, density, glucose, ketones, urobilinogen, and bilirubin in a urine sample. [00194] In some embodiments, a urine diagnostic test in a kit can include one or more UTI diagnostic tests. A UTI diagnostic test can include equipment necessary to perform a self-administered UTI diagnostic test for the detection of a UTI in urine. The UTI diagnostic tests can also include a plurality of leukocyte esterase and nitrite rapid screening urinary test strips. [00195] While cUTI is highly prevalent in particular patient populations, such as those with spinal cord injury and disease (SCI/D), neither consistent nor evidence-based guidelines exist for determining the likelihood of symptomatic UTI and/or selecting treatment for a UTI in patients. [00196] It has been shown that a mixed methods protocol integrating formal psychometric methods with large scale evidence gathering can be used to develop comprehensive diagnostic guidelines and treatment decision-making criteria for symptomatic UTI in a subject. It is therefore contemplated that diagnostic guidelines and treatment decision-making criteria described herein can be used in methods of determining the likelihood of a subject having symptomatic UTI and/or selecting treatment for a UTI in a subject in need thereof. [00197] Accordingly, additional embodiments described herein relate to a method of determining the likelihood of a symptomatic UTI in a subject. The method includes screening the subject for one or more urinary symptoms. [00198] Urinary symptoms can be screened in accordance with a method of determining the likelihood of a symptomatic UTI in a subject described herein either by a medical practitioner or screened and reported by the subject themselves. Screening of a subject for one or more urinary symptoms can be initiated by either the subject themselves or requested by a medical practitioner. In some cases, at least one urinary symptom is screened by a medical practitioner and at least one urinary symptom is screened/subjectively reported by the subject to the medical practitioner. [00199] In some embodiments, subjects are screened whenever urinary symptoms occur to determine whether to initiate treatment. In other embodiments, no urinary symptoms are apparent, but a subject is being monitored for the likelihood of symptomatic UTI, e.g., a subject may have a medical history of symptomatic UTI and/or a subject may be considered more susceptible to a severe urinary tract infection, such as those with SCI/D and/or neurogenic lower urinary tract dysfunction (NLUTD), previously referred to as a Neurogenic Bladder (NB). [00200] In some embodiments, screening for the presence or absence of one or more urinary symptoms in a subject can be achieved by providing a urinary symptom questionnaire or similar survey instrument (e.g., a digital survey instrument) for the subject to complete. In some embodiments, the urinary symptom questionnaire or similar survey instrument is a subjective urinary symptom questionnaire or survey instrument. The screening step can include having the subject answer questions from a urinary symptom screening questionnaire or survey instrument or marking a positive or negative response to a printed or digitally displayed list of urinary symptoms, and scoring/tallying answers and responses provided. Typically, the questionnaire or instrument survey is performed in private by the subject or a caregiver and the results kept confidential. [00201] As shown in Example 2 below, the presence and/or absence of a particular combination of urinary symptoms can correlate with a subject having a higher, moderate, low-moderate, lower, low, or lowest likelihood of symptomatic UTI. In particular embodiments, the urinary symptoms screened for in accordance with a method described herein can be selected from Action Needed, Bladder, Urine, and Other (previously referred to as Constitutional) urinary symptoms. [00202] Action Needed urinary symptoms screened for in a subject in accordance with a method described herein include bladder spasm frequency/discomfort, fever, increase in lower body tone or spasticity, difficulty ambulating, difficulty thinking/mental fogginess/forgetfulness, dizziness, headache, flushing of chest/neck/face, bladder discomfort, sweating, autonomic dysreflexia, abdominal/suprapubic pain and multiple sclerosis (MS) flare up. [00203] Bladder symptoms screened for in a subject in accordance with a method described herein include blood in urine, urinary urgency, incontinence/urine leakage, increase frequency of urination, sensation of urgency/empty bladder, inability to fully empty bladder, weak urine stream, change in quality of pain when passing urine, change in quality of pain during catheterization, increase in catheterization frequency, blood clots in urine, and reduced urine volume/catheterization volume. [00204] Urine symptoms screened for in a subject in accordance with a method described herein include malodorous urine, dark urine, and cloudy/sediment in urine. [00205] Other symptoms screened for in a subject in accordance with a method described herein include of increased fatigue/lethargy/weakness, chills, vomiting, loss of appetite, altered sleep patterns, muscle ache increase in positional pain, pain in the legs, change in bowel patterns, diarrhea, numbness/tingling in extremities, pain below level of injury, discharge/redness/sensitivity around catheter site, sense of burning in extremities/throughout the body, increase or decrease from normal blood pressure, malaise/feeling unwell, nausea, generalized abdominal discomfort or bloating, back pain, and irritability. [00206] Once a subject has been screened for one or more urinary symptoms, the presence or absence of each of the Action Needed, Bladder, Urine, and Other urinary symptoms screened are tallied to provide a cumulative score of the number and type of urinary symptoms endorsed and/or identified by the subject or health practitioner. A cumulative score can then be compared to predetermined value for each type of urinary symptom to identify the likelihood of symptomatic UTI in the subject. For example, a cumulative score can indicate that the subject has zero Action Needed urinary symptoms but has one each of Bladder, Urine, and Other urinary symptoms. A subject can be determined to have a higher likelihood of symptomatic UTI when the subject is identified through the screening step of having at least one Action Needed symptom and one or more Bladder or Urine symptoms above. For example, a subject can be determined to have a higher likelihood of symptomatic UTI when the subject is identified as having a fever (e.g., greater than 100.4^oF) and blood in urine. In addition to having an Action Needed urinary symptom, which and/or how many Bladder and Urine symptoms the subject has can further correlate to the likelihood of symptomatic UTI in the subject. [00207] In some embodiments, the subject is determined to have a moderate likelihood of symptomatic UTI when the subject is identified as having either: A) at least one Action Needed symptom and zero Bladder or U^^^^^^^^^^^^^^^^^^B) zero Action Needed symptoms, one or more Bladder symptoms, and one or more Urine symptoms. For example, a subject can be determined to have a moderate likelihood of symptomatic UTI when the subject is identified as having increase in tone or spasticity but no Bladder or Urine symptoms. In another example, a subject can be determined to have a moderate likelihood of symptomatic UTI when the subject is identified as having no Action Needed urinary symptoms but is experiencing urinary urgency and darker urine. [00208] In some embodiments, the subject is determined to have a low-moderate likelihood of symptomatic UTI when the subject is identified as having zero Action Needed symptoms, four or more Bladder symptoms, and zero Urine symptoms. For example, a subject can be determined to have a low-moderate likelihood of symptomatic UTI when the subject is identified as having a combination of blood in urine, urinary urgency, incontinence/urine leakage, and an increase frequency of urination but no Urine symptoms. [00209] In some embodiments, the subject is determined to have a lower likelihood of symptomatic UTI when the subject is identified as having either: A) zero Action Needed symptoms, zero Bladder symptoms, one or more Urine symptoms, and one or more Other symptoms^ or B) zero Action Needed symptoms, one to three Bladder symptoms, zero Urine symptoms and zero Other symptoms. For example, a subject can be determined to have a lower likelihood of having a symptomatic UTI when the subject is identified as having no Action Needed symptoms, coupled with blood in urine and/or urinary urgency and/or incontinence/urine leakage but no Urine symptoms listed above. In another example, a subject can be determined to have a lower likelihood of having a symptomatic UTI when the subject is identified as having no Action Needed symptoms, coupled with malodorous urine and/or dark urine and/or cloudy/sediment in urine but no Bladder urinary symptoms. [00210] In some embodiments, the subject is determined to have a low likelihood of symptomatic UTI when the subject is identified as having zero Action Needed symptoms, zero bladder symptoms, zero urine symptoms, but one or more Other symptoms. For example, a subject can be determined to have a low likelihood of having a symptomatic UTI when the subject is identified as having no Action Needed symptoms, zero Blood or Urine symptoms but suffers from the Other symptom of a loss of appetite. [00211] Finally, in some embodiments, the subject is determined to have a lowest likelihood of having a symptomatic UTI when the subject is identified as having zero Action Needed symptoms, zero Bladder symptoms, zero Urine symptoms, and zero Other symptoms, i.e. the subject is asymptomatic for each of the urinary symptoms described herein. [00212] It has also been shown that specific individual urinary symptoms that correlate to the likelihood of symptomatic UTI in a subject are dependent on whether a subject manages their bladder via urinary voiding (V), intermittent catheterization (IC), or indwelling catheterization (IDC). [00213] Therefore, in some embodiments, a subject screened for urinary symptoms in accordance with a method described herein is a subject managing their bladder via urinary voiding (V). The Action Needed symptoms screened for in a subject managing their bladder via urinary voiding are selected from the group consisting of bladder spasm frequency/discomfort, fever, increase in tone or spasticity, difficulty ambulating, difficulty thinking/mental fogginess/forgetfulness, sweating, autonomic dysreflexia and multiple sclerosis (MS) flare up. The Bladder symptoms for a subject managing their bladder via urinary voiding are selected from the group of blood in urine, urinary urgency, incontinence/urine leakage, increase frequency of urination, sensation of urinary urgency, inability to fully empty bladder, weak urine stream, and reduced urine volume/catheterization volume. The Urine symptoms for a subject managing their bladder via urinary voiding are selected from malodorous urine, dark urine, and cloudy/sediment in urine. Finally, for a subject managing their bladder via urinary voiding, the Other symptoms are selected from the group consisting of increased fatigue/lethargy/weakness, chills, vomiting, malaise/feeling unwell, and nausea. [00214] In other embodiments, the subject screened in accordance with a method described herein is a subject managing their bladder via intermittent catheterization (IC). For an IC subject, the Action Needed symptoms screened are selected from the group consisting of bladder spasm frequency/discomfort, fever, increase in lower body tone or spasticity, dizziness, headache, abdominal/suprapubic pain, and autonomic dysreflexia. The Bladder symptoms for a subject managing their bladder via IC are selected from the group consisting of blood in urine, urinary urgency, incontinence/urine leakage, change in quality of pain when passing urine, change in quality of pain during catheterization, increase in catheterization frequency, and decreased catheter volume/catheterization volume. The Urine symptoms for a subject managing their bladder via IC are selected from the group consisting of malodorous urine, dark urine, and cloudy/sediment in urine. The Other symptoms for a subject managing their bladder via urinary voiding IC are selected from the group consisting of fatigue/lethargy/weakness, loss of appetite, altered sleep patterns, muscle ache increase in positional pain, pain in the legs, change in bowel patterns, malaise/feeling unwell, nausea, generalized abdominal discomfort or bloating, back pain, and irritability. [00215] In still other embodiments, the subject screened in accordance with a method described herein is a subject managing their bladder via indwelling catheterization (IDC). For an IDC subject, the Action Needed symptoms are selected from the group consisting of bladder spasm frequency/discomfort, fever, increase in lower body tone or spasticity, flushing of chest/neck/face, bladder discomfort, sweating, autonomic dysreflexia, and abdominal/suprapubic pain. The Bladder symptoms for a subject managing their bladder via IDC are selected from the group consisting of blood in urine, urinary urgency, incontinence/urine leakage, and blood clots in urine. The Urine symptoms for a subject managing their bladder via IDC are selected from the group consisting of malodorous urine, dark urine, and cloudy/sediment in urine. The Other symptoms for a subject managing their bladder via IDC are selected from the group consisting of fatigue/lethargy/weakness, diarrhea, numbness/tingling in extremities, pain below level of injury, discharge/redness/sensitivity around catheter site, sense of burning in extremities/throughout the body, increase or decrease from normal blood pressure, generalized abdominal discomfort or bloating, back pain, and irritability. [00216] In some embodiments, subjects screened for urinary symptoms in accordance with a method described herein can include any subject having, or at risk of having or developing, symptomatic UTI. For example, in some embodiments, the subject can have a spinal cord injury or disorder (SCI/D). However, methods described herein are not limited to use on subjects perceived to be at risk of symptomatic UTI, as the methods may be directed to any subject (e.g., an asymptomatic subject) that may benefit from a determination of symptomatic UTI likeliness as provided by a medical practitioner. [00217] In some embodiments, subjects in accordance with a method described herein can include a subject that manages their bladder through, at least in part, the use of catheterization. For example, a subject may use intermittent catheterization (IC) or indwelling catheterization (IDC) for bladder management. In some embodiments, a subject managing their bladder using catheterization may be at risk of a Catheter-Associated Urinary Tract Infection (CAUTI). CAUTI’s occur when bacteria or yeast travel along the catheter and cause an infection in a subject’s bladder or kidney. The most important risk factor for developing a catheter-associated UTI (CAUTI) is prolonged use of the urinary catheter. [00218] In some embodiments, a subject of a method of determining the likelihood of a symptomatic UTI in a subject described herein can include a subject having a NLUTD. An NLUTD-subject can utilize a urinary catheter which may be used: (a) on an intermittent basis ^^^^5^^^^^^^%^^^^^%^^^^^^^^^^^^^^^^^^^^^^^^ ^^^^^^^^^^^^^^ ^^^^^^^^^^^^^^^^^%^^^^^^^- and immediately post-^^^^^^^^^^^^ ^^^^^^%^^^^^^^^ ^^^^^^^^^^^^^^^+^^^^.g. post-^^^^^^^^^^^^^^^ ^^^ continuous or chronic long term (30 days or more, e.g. SCI/Ds and in Long Term Care Facilities (LTCFs)). An indwelling catheter that is left in place for a period of time is in general attached to a sterile container to collect the urine. The most commonly used Foley indwelling catheter is a soft silicone or latex tube that is inserted into the bladder through the urethra to drain the urine and is retained by a small balloon inflated with air or liquid. Urinary catheters come in a large variety of sizes, materials (latex, silicone, uncoated or coated with other materials such as silicone, hydrogel, antibacterial agents, etc.), and types (Foley catheter, straight catheter, Coude-tip catheter, etc.). Catheters are generally placed into the bladder through the urethra, but in some cases, an NLUTD-subject of the present invention may have a suprapubic indwelling catheter that is placed directly into the bladder through a surgically prepared opening (stoma) in the abdomen above the pubic bone. Catheters can be replaced at a variety of frequencies but are generally replaced about once a month. [00219] While subjects with NLUTD can result from any trauma or disease of the brain or spinal cord, people with SCI/D, multiple sclerosis (MS), and spina bifida (SB) are heavily affected. Therefore, in specific embodiments, subjects in accordance with a method described herein can include individuals with NLUTD due to SCI/D, MS or SB. [00220] Other embodiments described herein relate to a method of selecting a treatment for a UTI in a subject. The method includes screening the subject for one or more urinary symptoms selected from the group consisting of Action Needed, Bladder, Urine, and Other urinary symptoms. Once the subject has been screened for one or more urinary symptoms, a treatment is selected based on the likelihood of symptomatic UTI (i.e., a higher, moderate, low-moderate, lower, low, or lowest likelihood) in the subject as determined by the presence/absence of urinary symptoms and/or particular combinations thereof, as described above. [00221] In some embodiments, methods related to determining the likelihood of a symptomatic UTI in a subject and/or selecting treatment for a UTI described herein are performed, at least in part, using a computer process. For example, the screening and/or treatment selection steps can be utilized as part of an algorithm, such as an algorithm implemented in a computer program. In some embodiments, an algorithm implemented in a computer program can be run by a health care provider/practitioner or the subject themselves. [00222] In an exemplary embodiment, the algorithm can be derived from the decision- making algorithm flow diagram illustrated in Fig.6 and further summarized in Table 3 in Example 2 below. As shown in Fig.6, a decision-making algorithm can include decision points that are used to determine the likelihood of symptomatic UTI in a subject following the screening of urinary symptoms and/or guide the selection of appropriate treatment based on the determined likelihood of symptomatic UTI in a subject. [00223] In some embodiments, the subject is determined to have a higher likelihood of symptomatic UTI, and the selected treatment includes administering to the subject a therapeutically effective amount of an antimicrobial agent (e.g., an antibiotic agent) and/or an antispasmodic agent. [00224] It is contemplated that an LBP comprised of a combination of Lacticaseibacillus rhamnosus and/or Lactobacillus crispatus is an appropriate treatment for a subject having a mid-tier likelihood of symptomatic UTI. Therefore, in particular embodiments, for a subject determined to have a moderate, low-moderate, or lower likelihood of symptomatic UTI, the selected treatment can include the administration of a therapeutically effective amount of an LBP comprising Lacticaseibacillus rhamnosus and/or Lactobacillus crispatus. An LBP combination therapy treatment can be administered to the subject by a health care practitioner and/or self-administered by the subject. Embodiments including the self-administration of an LBP treatment can include further providing to the subject preparation and/or administration instructions for the selected LBP treatment. If urinary symptoms persist or worsen medical assistance outside of the LBP combinatory treatment can be sought by the subject. [00225] Finally, a subject determined to have a low or a lowest likelihood of symptomatic UTI as described herein, and the treatment includes continued monitoring of urinary symptoms in the subject. Typically, the continued monitoring of urinary symptoms can include self-monitoring urinary symptoms by the subject. Where continued self- monitoring is selected, the method can further include providing to the subject instructions for accurately self-monitoring urinary symptoms. Alternatively, or in addition to self- monitoring by the subject, a health care practitioner can continue to monitor one or more urinary symptoms in the subject as needed. Continued monitoring can be performed for an amount of time deemed suitable by a health care practitioner to confirm that a subject remains at a low or a lowest likelihood of symptomatic UTI or to select another appropriate treatment if the likelihood of a symptomatic UTI increases in the subject. [00226] Additional embodiments described herein relate to a method of treating or preventing a UTI in a subject using a combination therapy. The method includes administering to the subject a therapeutically effective amount of a live biotherapeutic product (LBP), wherein the LBP includes a combination of probiotic bacterial species Lacticaseibacillus rhamnosus and Lactobacillus crispatus. [00227] The phrase “combinatorial therapy” or “combination therapy” embraces the administration of Lacticaseibacillus rhamnosus and Lactobacillus crispatus described herein as part of a specific treatment regimen intended to provide beneficial effect from the co- action of these probiotic therapeutic agents. Administration of these probiotic agents in combination is typically carried out over a defined period (usually minutes, hours, days or weeks depending upon the type and/or severity of the UTI being treated). [00228] In particular embodiments, a subject administered a combination therapy described herein can be determined to have a moderate, low-moderate, or lower likelihood of symptomatic UTI, e.g., using a method described herein. For example, a subject can be identified using the decision-making algorithm illustrated in Fig.1, as having a moderate, low-moderate, or lower likelihood of symptomatic UTI prior to administering an LBP combination therapy to the subject. [00229] In other embodiments, a combination therapy described herein can be administered to any subject in need thereof, (e.g., as determined by a health practitioner) and not necessarily a subject selected for LBP combination treatment using the methods described above. For example, a subject in need of a combination therapy described herein may suffer from, or have an increased risk or likelihood of, a urinary tract infection (UTI) and/or is more susceptible to a severe urinary tract infection. A more severe form of UTI can be a UTI exhibiting one or more urinary symptoms that are problematic and/or painful to a subject. In some embodiments, a subject may not have a currently diagnosed UTI but may be considered at an increased risk of a UTI. An increased risk refers to a higher likelihood or percent possibility of having a UTI in comparison with a control subject. In some embodiments, a control subject can include a subject who is not at an increased risk of UTI or a healthy subject. [00230] In some embodiments, a subject treated in accordance with a method described herein may have either an uncomplicated UTI or a complicated UTI (cUTI). UTIs can be differentiated between uncomplicated or simple and complicated UTIs by a medical practitioner based on risk factors, clinical presentation, and potential complications. An uncomplicated UTI can include an infection of the urinary tract due to appropriate susceptible bacteria, typically an infection in an afebrile non-pregnant immune-competent female subject. UTIs can be complicated by several risk factors leading to treatment failure, repeat infections, or significant morbidity and mortality with a poor outcome. A complicated UTI can include any UTI other than an uncomplicated UTI. Therefore, UTIs in immunocompromised subjects, males, pregnant patients, and those associated with fevers, stones, sepsis, urinary obstruction, catheters, or involving the kidneys can be considered complicated UTIs. In some embodiments, a subject may suffer from recurrent UTIs. In some cases, a recurrent UTI can be considered an uncomplicated UTI. For example, a recurrent UTI can be considered uncomplicated provided there is a prompt response to first-line antibiotics without any long- term sequela. On the other hand, recurrent UTI despite adequate treatment can be considered a complicated UTI. [00231] In some embodiments, a UTI treated in accordance with a method described herein can be diagnosed in a subject using laboratory diagnostic methods that may include culturing urine samples obtained from the subject. In some embodiments, any well-known UTI screening methods can be used in addition to the methods described herein to confirm or aid in diagnosing UTI infection, or even the likelihood thereof, in a subject. Additional non- limiting screening methods for UTI can include the use of urine culture, blood culture, a complete blood count (CBC), ultrasound, intravenous pyelogram (IVP), and cystoscopy. [00232] In some embodiments, a subject in need of UTI treatment or prevention described herein can be identified using one or more urine tests on urine obtained from the subject. A variety of methods are known to those skilled in the art for obtaining a urine sample. Urine can be collected from an individual by suprapubic aspiration. This method represents the ideal method for obtaining a urine sample. However, it is not performed routinely in clinical practice in which urine samples are generally obtained after natural ^^^^^^^^^^^^^^^^^^^^^^^^^^^%^^^^^^^^^%^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ormal urethral organisms occurs. A standard method for obtaining a urine sample can be referred to as the clean-catch sample method. To obtain an untainted urine sample, doctors usually request a so-called midstream, or clean-catch, urine sample. To provide this, the subject washes the area from which urine will issue, urinates a small amount into the toilet for a few seconds and then stops, position the container to catch the middle portion of the stream, urinates until the collection cup is halfway full (about 2 ounces), and then removes the cup. The collection cup should then be sealed with a cap and given to the doctor or sent to the laboratory for analysis. [00233] Alternately, urine can be collected with a catheter. Some patients (e.g., small children, elderly people, or hospitalized patients) cannot provide a urine sample. In such cases, a catheter may be inserted into the bladder to collect urine. This is the best method for providing a contaminant-free sample but has the disadvantage of possibly introducing or spreading infection and discomfort to the subject. [00234] The urine sample may be pretreated as necessary by dilution in an appropriate buffer solution and concentrated or fractionated by any number of methods including but not limited to ultracentrifugation, fractionation by fast performance liquid chromatography (FPLC), or precipitation. Any of a number of standard aqueous buffer solutions at physiological pH, such as phosphate, Tris, or the like, can be used. [00235] Once a sample has been obtained, an analytic device is used to measure the levels of bacterial species. The analytic device can be either a portable or a stationary device. In addition to including equipment used for detecting the bacterial species, the analytic device can also include additional equipment to provide physical separation of analytes prior to analysis. For example, if the analyte detector is an immunoassay, it may also include an ion exchanger column chromatography to purify the proteins from urine before the specific detection of bacterial species by immunoassay. Methods for detecting bacterial species are readily known to those skilled in the art. For example, urine samples can be assayed using urinalysis, and/or urine culture. An alternate method for determining the predominant bacterial species is by using a polymerase chain reaction (PCR)-based assay, such as multiplex PCR. [00236] Once the levels of bacterial species have been determined, they can be displayed in a variety of ways. For example, the levels of specific bacterial species can be displayed graphically on a display as numeric values or proportional bars (i.e., a bar graph) or any other display method known to those skilled in the art. The graphic display can provide a visual representation of the amounts of the various bacterial species in the samples being evaluated. In addition, in some embodiments, the analytic device can also be configured to display a comparison of the levels of bacterial species in the subject’s urine to a control value based on levels of bacterial species in a comparable urine sample, urine samples from a reference cohort, or a standard numerical reference. [00237] In some embodiments, one or more urine tests can be selected from urinalysis (UA), urine culture, and susceptibility tests. A urinalysis can involve performing several tests on urine. These tests include an examination of the urine under a microscope and chemical tests that check the urine for various substances and/or microorganisms. A urine dipstick is one type of chemical test that may be performed during a urinalysis. A urine culture test allows bacteria from the urine of a subject to be grown in a controlled laboratory environment and can be used to identify the specific species of bacteria in the subject’s urobiome. Susceptibility testing may be performed once bacteria have grown in the urine culture. Those bacteria are exposed to various antibiotics to identify the most effective one to use in treating a subject identified as in need of urobiome dysbiosis treatment. [00238] In certain embodiments, the urine test includes UA. UA can be performed routinely as necessary, for example as determined necessary by a medical practitioner. In some embodiments, urine analysis can be performed on a urine sample obtained from a subject about every 2 to 3 days. [00239] In other embodiments, a subject treated in accordance with a method described herein may be asymptomatic for a UTI. For example, a subject utilizing intermittent catheterization (IC), may not have any Action Needed or Bladder urinary symptoms indicative of a symptomatic UTI. In certain embodiments, where the therapeutic method relates to the prevention of UTI in a subject, the subject does not have a UTI (e.g., a subject can test negative for a UTI using laboratory diagnostic methods) prior to administration of an LBP combination therapy. [00240] The probiotic(s) of a LBP combination therapy for use in a composition or method described herein can include any beneficial symbiotic strains of Lacticaseibacillus rhamnosus and Lactobacillus crispatus, which are applicable to the prevention and or treatment of UTI in a subject. Typically, the probiotics of the present invention are viable when administered and when reaching the desired site of administration. The probiotics of the present invention can be administered together as a blend or mixture in a single dosage form or can be administered in separate dosage forms at separate times. In some embodiments, when the probiotics are taken via intravesicular administration, such as bladder instillation, the probiotics are capable of successfully colonizing the lower urinary tract of the subject. [00241] “Combinatorial therapy” or “combination therapy” is intended to embrace administration of these bacterial probiotic agents in a sequential manner, that is, wherein each agent is administered at a different time, as well as administration of at least these two probiotic agents, in a substantially simultaneous manner. Substantially simultaneous administration can be accomplished, for example by administering to the subject an individual dose having a fixed ratio of each therapeutic agent or in multiple, individual doses for each of the probiotic agents. Sequential or substantially simultaneous administration of each probiotic agent can be achieved by any appropriate route including, but not limited to, intravesicular routes, intravaginal routes, intraurethral, routes oral routes, intravenous routes, intramuscular routes, direct absorption through mucous membrane tissue and combinations thereof. Probiotic agents described herein can be administered by the same route or by different routes. [00242] Accordingly, combination therapies for the treatment or prevention of a UTI described herein can include the sequential administration of a Lacticaseibacillus rhamnosus and Lactobacillus crispatus. In some embodiments, both the Lacticaseibacillus rhamnosus and Lactobacillus crispatus are administered together to a subject for the entire course of the subject’s treatment. In other embodiments, the dosing regimen of each of the combination of probiotic bacteria to a subject may overlap for a period of time over the course of the subject’s treatment. [00243] Lacticaseibacillus rhamnosus and Lactobacillus crispatus strains for use in compositions and methods described herein can include both naturally occurring strains as well as genetically engineered strains. In addition to known species and strains of Lacticaseibacillus rhamnosus and Lactobacillus crispatus, newly identified strains from nature and mutant strains derived from known or newly identified strains can be used in a method or composition of the present invention. Mutants of a parental strain of Lacticaseibacillus rhamnosus and/or Lactobacillus crispatus that have the identifying characteristics of a Lacticaseibacillus or Lactobacillus suitable for use in a composition or method of the present invention can be obtained by, for example, subjecting a parental strain to at least one round of chemical and/or radiation mutagenesis, to increase the rate of mutagenesis, thereby increasing the probability of obtaining a microorganism having improved desired characteristics. It will be obvious to one of skill in the art that mutant microorganisms for use in the present invention also include microorganisms that can be obtained by genetically engineering microorganisms to, for example, have increased epithelial cell cohesion values. As used herein, a “mutated microorganism” is a mutated parental microorganism in which the nucleotide composition of such microorganism has been modified by mutation(s) that occur naturally, that are the result of exposure to a mutagen, or that are the result of genetic engineering. [00244] Various Lacticaseibacillus rhamnosus and Lactobacillus crispatus existing in the human urobiome may have individual differences in resistance to pathogenic bacteria. Suitable Lacticaseibacillus rhamnosus and Lactobacillus crispatus strains for use in the compositions and methods described herein include those having favorable acid-producing ability, H₂O₂-producing ability, and adhesive ability to epithelial cells in and/or near the urinal tract. The successful colonization of a Lacticaseibacillus rhamnosus and Lactobacillus crispatus strain may be a key factor in the therapeutic effect of the bacterial strain. In addition, it has been shown that H2O2-producing Lacticaseibacillus/Lactobacillus species can protect from pathogenic infection, and acids and some antimicrobial agents produced by Lacticaseibacillus/Lactobacillus metabolism can also effectively inhibit the growth of other bacteria. [00245] Any Lacticaseibacillus or Lactobacillus species described herein can include a Lacticaseibacillus or Lactobacillus strain having 95% sequence homology to the 16S rRNA gene sequence of any of the identified species. For example, methods used to differentiate between Lactobacillus strains include Rep-PCR, as described in Antonio & Hillier, J Clin. Microbiol.2003, 41: 1881-1887, multilocus sequence typing (MLST), originally developed to identify strains of pathogens (see, e.g., Maiden, M. C., et. al.1998, Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc. Natl. Acad. Sci. USA., 95:3140-2145), and whole genome sequencing. [00246] In some embodiments, Lacticaseibacillus rhamnosus strains for use in a composition or method described herein includes the Gorbach-Goldin (LGG) strain of Lacticaseibacillus rhamnosus (deposited in the American Type Culture Collection (ATCC) under ATCC number ATCC 53103). Lacticaseibacillus rhamnosus can also include Lacticaseibacillus rhamnosus GR-1 (also referred to as Lacticaseibacillus rhamnosus GR-1 (LGR-1). [00247] Lactobacillus crispatus strains for use in compositions and methods described herein can include, but are not limited to, Lactobacillus crispatus SJ-3C, Lactobacillus crispatus 262-1, Lactobacillus crispatus CTV-05 (LACTIN-V), Lactobacillus crispatus M247, and Lactobacillus crispatus Bi16. [00248] In certain embodiments, Lactobacillus crispatus for use in a composition and/or method described herein includes Lactobacillus crispatus SJ-3C, Lactobacillus crispatus 262- 1, Lactobacillus crispatus CTV-05 (LACTIN-V). Lactobacillus crispatus CTV-05 is hydrogen peroxide-producing vaginal Lactobacillus that is part of the natural vaginal microbiome of many healthy women designated the PubChem Identifier number 482028468. Lactobacillus crispatus SJ-3C (SJ-3C) cells are deposited in the American Type Culture Collection (ATCC) under ATCC number PTA-10138. An isolated Lactobacillus crispatus strain named Lactobacillus crispatus 262-1 is deposited in the China General Microbiological Culture Collection Center with an accession number of CGMCC No.6469. [00249] Lacticaseibacillus rhamnosus and Lactobacillus crispatus described herein for use in a method described herein can be formulated in a pharmaceutical composition. Consequently, additional embodiments described herein relate to a pharmaceutical composition for the treatment or prevention of UTI. The pharmaceutical composition can comprise an LBP, wherein the LBP includes a combination of Lacticaseibacillus rhamnosus and Lactobacillus crispatus. [00250] In particular embodiments, the Lacticaseibacillus rhamnosus of a pharmaceutical composition is Lacticaseibacillus rhamnosus GG (LGG). In particular embodiments, the Lactobacillus crispatus can be selected from one or more of the group consisting of Lactobacillus crispatus CTV-05, Lactobacillus crispatus SJ-3C, and Lactobacillus crispatus 262-1. [00251] A pharmaceutical composition including an LBP combination therapy of the present invention can further include a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutically acceptable carrier is formulated for intravesical, topical, intravaginal, and/or intraurethral administration. In an exemplary embodiment, the composition is formulated for intravesical administration and/or as an intravaginal or intraurethral suppository. [00252] A pharmaceutically acceptable carrier for use in an LBP containing pharmaceutical composition described herein can include any suitable inactive pharmaceutically acceptable excipient (i.e., carriers, solvents, stabilizers, adjuvants, diluents, etc.) known in the art. Pharmaceutically acceptable excipients are determined in part by the particular composition being administered, as well as by the particular method used to administer the composition. Accordingly, there exists a wide variety of suitable formulations of pharmaceutical compositions (see, e.g., Remington’s Pharmaceutical Sciences). The pharmaceutical compositions should generally be formulated to achieve a physiologically compatible pH and may range from a pH of about 3 to a pH of about 11, preferably about pH 3 to about pH 7, depending on the formulation and route of administration. In alternative embodiments, it may be preferred that the pH is adjusted to a range from about pH 5.0 to about pH 8. More particularly, the pharmaceutical compositions may comprise a therapeutically or prophylactically effective amount of at least one compound as described herein, together with one or more pharmaceutically acceptable excipients. Optionally, the pharmaceutical compositions may comprise a combination of the probiotic agents described herein or may include one or more additional active therapeutic ingredients, agents, or adjuvants useful in the treatment or prevention of a UTI. [00253] Formulations for administering an LBP combination therapy in a method described herein typically include an adequately buffered solution. An adequately buffered solution should be considered to reduce the event of drug precipitation. Formulations may include for example, sterile water, instillation buffers such as Tris buffer, phosphate-buffered saline (PBS) and saline. An LBP combination therapy and pharmaceutical composition thereof can be administered in accordance with a therapeutic method described herein, may be formulated for administration by a variety of routes. In particular embodiments, compositions are formulated in a manner suitable for intravesicular administration. In some embodiments, formulations for intravesicular administration can include an adequately buffered normal saline solution. In some embodiments, formulations for intravesicular administration of one or more therapeutic agents described herein can include a citric acid buffered normal saline solution. [00254] In some embodiments, agents and compositions for use in an LBP combination composition described herein can be formulated into a unit dosage form. Non-limiting examples of dosage forms of which the therapeutic agents and any additional material such as a carrier can be incorporated include capsule, chewable tablet, swallowable tablet/pill, buccal tablet, coated tablet, troche, powder, lozenge, soft chew, solution, suspension, spray, extract, tincture, oil, decoction, infusion, syrup, elixir, wafer, food product, and combinations thereof. The dosage forms can comprise ingestible carriers, non-limiting examples of which include solid or liquid filler diluents, encapsulating substances, and mixtures and combinations ^^^^^^^^^^^%^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^%^^^^^^^^^^^^^^%^^^^^^^^ ^^^^^^^^^^^^^^^^^^^^^^%^^^^^^^^^^^^^^^^^^^%^^^^^^^^^^^^^^^^^^^^^^^%^^^^^^%^^^^^^^^^^^^^^^%^^-free ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^%^^%^^^^^^^^^^^^^^^^^^^^^^^^^%^^%^^^^^^ flavoring ^%^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ [00255] In some embodiments, agents and compositions for use in an LBP combination composition described herein can be formulated into a suppository form (e.g., a vaginal or urethral suppository form). A suppository formulation can typically include active therapeutic agents in combination with a base made from ingredients including but not limited to cocoa butter, polyethylene glycol (PEG) and fatty acid ester of PEG, hydrogenated vegetable oils, glycerinated gelatin, and similar recognized non-active ingredients. [00256] In some embodiments, a pharmaceutically acceptable excipient for use in an LBP combination composition described herein includes a diluent. A diluent can be maltodextrin, pre-gelatinized starch, lactose, Pharmasperse excipient blend, mannitol, xylitol, microcrystalline cellulose, sugar or a combination thereof. In other embodiments, an inactive bulking agent can be used in combination with another diluent. [00257] In some embodiments, the LBP combination composition is a dried formulation. For example, the composition can be dried via lyophilization (e.g., freeze drying). In some embodiments, a Lactobacillus dried powder is diluted with an inactive excipient by between 3-fold and 10-fold. In other embodiments, the Lactobacillus dried powder can be combined with an inactive excipient at a ratio of powder to inactive excipient of between 1:1 and 1:12 w/w. In some embodiments, a maltodextrin or pre-gelatinized starch can be used as a diluent to dilute a Lactobacillus dried powder formulation. For example, in some embodiments, a Lactobacillus dried powder formulation can be combined with maltodextrin at a ratio of dried powder to maltodextrin of between 1:1 and 1:10 w/w. The potency of the diluted Lactobacillus dried powder, referred to as the drug product, can be between 10⁸ CFU/g and 10¹¹ CFU/g. In some embodiments, the drug product can be greater than 10¹¹ CFU/g. [00258] In some embodiments, the LBP combination composition is in a single dose form appropriate for intravesical, topical, intravaginal, and/or intraurethral administration. For example, the composition can be packaged in drug product dosages of between about 1 mg and 1 g. In some embodiments, the composition can be packaged in drug product dosages of between about 100 mg and 800 mg. [00259] In certain embodiments, at least one of the LBPs of the combination therapy is administered via intravesicular administration. In some embodiments, a first LBP is administered systemically, and a second LBP is administered intravesicularly. In particular embodiments, each of the LBPs are administered to a subject via intravesicular administration. In some embodiments, each of the first and second LBPs can be administered systemically, intravesicularly, intravaginally, or via intraurethral administration as needed over the course of a combination therapy described herein. [00260] Intravesicular administration of an LBP typically involves delivery of a liquid therapeutic directly into the bladder. In some embodiments, intravesicular administration includes instillation of one or more therapeutic agents directly into the bladder via insertion of a urethral catheter. Instilled therapeutic agents described herein should be kept in the bladder for a period of time to ensure a therapeutically effective outcome. In some embodiments, the instillation can be kept in the bladder (i.e. dwell time) for about 5 minutes, about 10 minutes, about 20 minutes, about 30 mins, about 45 minutes, about 1 hour about 1.5 hours, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, about 8 hours, or more. In exemplary embodiments, an antibiotic is instilled in the bladder of the subject and allowed to dwell about 1 hour. In some embodiments, for example in a subject undergoing intermittent catheterization (IC), LBP can be instilled in the bladder after urine drainage and remain in the bladder until the next catheterization and drainage. [00261] In some embodiments, therapeutic agents of a combinatory therapy described herein are self-administered, or administered with caregiver assistance, and don’t require a medical professional’s presence. Standardized instructions on administration, including a tutorial on use and preparation of the agents and/or a step-by-step video can be provided to the subject in need thereof. In some embodiments, each of the agents in the combination therapy are self-administered via intravaginal administration (e.g., vaginal suppository), intraurethral administration (e.g., urethral suppository) and/or via intravesicular administration (e.g., bladder instillation). [00262] Individual therapeutic agents and/or a pharmaceutical composition described herein for use in the treatment or prevention of a UTI can be administered in accordance with the methods at any frequency as a single dose or multiple doses, e.g., one, two, three, four, five, or more times hourly, daily, weekly, monthly, or annually or between about 1 to 10 days, weeks, months, or for as long as appropriate. Exemplary frequencies are typically from 1-7 times, 1-4 times, 1-3 times, 2-times or once, daily, weekly or monthly. Timing of administration can be dictated by the UTI, symptoms, pathology or adverse side effect(s) to be treated. For example, a therapeutically effective amount of a LBP combination therapy or pharmaceutical composition thereof described herein can be administered to the subject substantially contemporaneously with, or within about 1 minute to about 60 minutes, hours, days, or even weeks from the onset of a symptom related to UTI in a subject. In other embodiments, a therapeutically effective amount can be administered to the subject substantially contemporaneously with, or within about 1-60 minutes, hours, days, or weeks or of the completion of a urinalysis assay and/or urinary symptom screening that determines that the subject has a moderate, low-moderate, or lower likelihood of symptomatic UTI, as described above. [00263] Doses may vary depending upon whether the treatment is therapeutic or prophylactic, the onset, progression, severity, frequency, duration, probability of or susceptibility of a particular symptom, the type of UTI pathogenesis to which treatment is directed, clinical endpoint desired, previous, simultaneous or subsequent treatments, general health, age, gender or race of the subject, bioavailability, potential adverse systemic, regional or local side effects, the presence of other disorders or diseases in the subject, and other factors that will be appreciated by the skilled artisan (e.g., medical or familial history). Dose amount, frequency or duration may be increased or reduced, as indicated by the clinical outcome desired, status of the infection, symptom or pathology, any adverse side effects of the treatment or therapy. The skilled artisan will appreciate the factors that may influence the dosage, frequency and timing required to provide an amount sufficient or effective for providing a prophylactic or therapeutic effect or benefit. The exact dosage will be determined by the practitioner, in light of factors related to the subject that requires treatment. Dosage and administration are adjusted to provide sufficient levels of the active therapeutic agents or to maintain the desired effect. It will be appreciated that treatment as described herein includes preventing urobiome dysbiosis or related disease or disorder, ameliorating symptoms, slowing disease progression, reversing damage, or curing a disease. [00264] The dosage of therapeutics for the treatment or prevention of a UTI may range broadly, depending upon the desired effects and the therapeutic indication. Alternatively, dosages may be based and calculated upon the body surface area (BSA) or body weight of the patient as a useful way to mitigate patient size variation in medication regimens, as understood by those of skill in the art. Although the exact dosage will be determined on a drug-by-drug basis, in most cases, some generalizations regarding the dosage can be made. The daily dosage regimen for an adult human patient may be, for example, a dose of between about 0.01 mg and about 3000 mg of the active ingredient, preferably between 1 mg and 700 mg, e.g., 5 to 200 mg. The dosage may preferably depend upon the body weight of the patient. For example, the dosage may be between 0.01 mg/kg and 3000 mg/kg of the active ingredient, preferably between 1 mg/kg and 1000 mg/kg, e.g., 5 to 200 mg/kg or 10 to 100 mg/kg. The dosage may be a single one or a series of two or more given in the course of one or more days, as is needed by the subject. In some embodiments, the therapeutic agent(s) will be administered for a period of continuous therapy, for example for a week or more, or for months or years. [00265] In some embodiments, an LBP, including a combination of probiotic Lacticaseibacillus rhamnosus and Lactobacillus crispatus species can be administered at a concentration of from about 1 x 10³ to about 1 x 10¹⁴ colony forming units (cfu) of probiotic, alternatively from about 1 x 10 to about 1 x 10¹⁴ cfu of probiotic, alternatively from about 1 x 10⁷ to about 1 x 10¹⁴ cfu of probiotic, alternatively from about 1 x 10⁹ to about 1 x 10¹² cfu of probiotic, and alternatively from about 1 x 10¹⁰ to about 1 x 10¹² cfu of probiotic, and alternatively from about 1 x 10¹¹ to about 1 x 10¹² cfu of probiotic, per dose or per day. [00266] The therapeutically effective amount of an LBP or pharmaceutical composition thereof administered to a subject as described herein can include an amount of LBP that is effective to achieve alleviation of symptoms of the health problems, conditions, and/or diseases managed by the methods and of the present invention. The amount of the respective LBP administered will, of course, be dependent on the subject and disease/disorder state being treated, the severity of the affliction (i.e., UTI), the particular combination of agents included in a combination therapy as described herein, the manner and schedule of administration, and the judgment of the prescribing health practitioner. [00267] In some embodiments, the therapeutically effective amount of a LBP combination therapy described herein can include the amount effective to prevent, inhibit and/or reduce the frequency, degree of severity and/or impact one or more uropathogenic bacteria related LUTS related to a UTI in the subject. Exemplary uropathogenic bacterial species responsible, at least in part, for LUTS or UTI in a subject can include uropathogenic Escherichia coli (UPEC), as well as Shigella and Aerococcus, Klebsiella, Proteus, Pluralibacter, and Enterococcus uropathogenic bacterial species. [00268] In some embodiments, the therapeutically effective amount of an LBP combination therapy is the amount required to successfully colonize/recolonize the lower urinary tract with the LBP, following treatment. In some embodiments, successful colonization/recolonization with an LBP can include at least a 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or more increase in the abundance of the LBP in the urobiome of a subject compared to a control amount. A control amount can include a baseline abundance of an LBP measured in the subject’s urobiome prior to the administration of the combination of therapeutic agents. In some embodiments, the baseline measurement for a particular LBP can be zero and in which case the increase in the abundance of the LBP will be absolute. [00269] A therapeutically effective amount of an LBP combination therapy described herein can include the amount required for successful (e.g., robust) colonization or recolonization of the Lacticaseibacillus rhamnosus and Lactobacillus crispatus probiotic bacterial species in the urinary tract of the subject. In some embodiments, successful colonization of the urobiome can be identified in a subject by measuring the amount of a therapeutic probiotic in a sample obtained from the bladder of a subject following treatment. In some embodiments, the successful colonization/recolonization is the presence of a threshold value of the measured Lacticaseibacillus rhamnosus and Lactobacillus crispatus probiotic species and/or a threshold value of measured uropathogen in the urobiome of the subject. The threshold value(s) may be identified using data taken from subjects previously treated using a combination therapy described herein, wherein the threshold value(s) correlated to a therapeutically effective treatment. For example, successful colonization, or recolonization, of a probiotic bacterial species in the urinary tract of the subject can be defined as the urobiome of the urinary tract having a measured Lacticaseibacillus rhamnosus and/or Lactobacillus crispatus probiotic bacterial density of about 10³ to about 10⁴ CFU/m. [00270] The therapeutically effective amount of a combination therapy described herein can be measured and/or defined in numerous ways. In some embodiments, the therapeutic amount of an LBP combination therapy described herein can be the amount required to reduce the abundance of native and/or uropathogenic bacterial species in the urinary tract and to allow colonization or recolonization of the LBP, e.g., beneficial probiotic Lacticaseibacillus rhamnosus and Lactobacillus crispatus species, in the urinary tract of the subject. In some embodiments, the therapeutic effectiveness of an LBP combination therapy described herein can be measured by determining the likelihood of a symptomatic UTI in a subject before and after treatment, wherein a reduction in the likelihood of a symptomatic UTI as a result of treatment can be indicative of an effective therapy. [00271] The effectiveness of a particular combination therapy described herein can also be determined by measuring the amount of LBP colonization in the urobiome of a subject following administration of the combination therapy and comparing an increase in the amount of LBP colonization in the sample to a threshold amount or a ratio of uropathogen to LBP, (e.g., a probiotic bacterial species), and identifying a subject having an insufficient amount of probiotic bacterial colonization. In some embodiments, the therapeutically effective amount is the amount required to improve the ratio of uropathogen(s) to a Lacticaseibacillus rhamnosus and/or Lactobacillus crispatus (i.e., U/L ratio) by about 25% in the urobiome of a subject compared to a control. The control can include a baseline ratio of uropathogen to a particular probiotic species measured prior to the administration of the LBP probiotic combination therapy. [00272] In some embodiments, a method of treating or preventing UTI in subject can further include administering to the subject one or more additional therapeutic agents. For example, additional therapeutic agents can include one or more probiotic bacterial species, antimicrobial agents and/or antispasmodic agents. The one or more additional therapeutic agents are not limited to administration via the same route as Lacticaseibacillus rhamnosus and Lactobacillus crispatus and may be administered by any suitable route, such as but not limited to, intravaginally, intraurethral administration, intravesically, orally or systemically. For example, an antimicrobial agent can be administered to a subject systemically either before or after the intravesicular and/or intravaginal administration of a LBP combination therapy described herein, if need be, e.g., as determined necessary by a medical practitioner. [00273] Additional non-limiting examples of probiotics useful with a method of the present invention for the treatment of a UTI in a subject include bacteria selected from the group consisting of Lactobacillus gasseri, Lactobacillus Jensenii Lactobacillus iners, Lactobacillus reuteri, Lactobacillus fermentum, Lactobacillus plantarum, Lactobacillus salivarius, Lactobacillus helveticus, Lactobacillus casei, Lactobacillus bulgaricus, Lactobacillus sporogenes, Lactococcus lactis, Bifidophilus infantis, Streptococcus thermophilous, Bifodophilus longum, Bifidobacteria bifidus, Arthrobacter agilis, Arthrobacter citreus, Arthrobacter globiformis, Arthrobacter leuteus, Arthrobacter simplex, Azotobacter chroococcum, Azotobacter paspali, Azospirillum brasiliencise, Azospriliium lipoferum, Bacillus brevis, Bacillus macerans, Bacillus pumilus, Bacillus polymyxa, Bacillus subtilis, Bacteroides lipolyticum, Bacteroides succinogenes, Brevibacterium lipolyticum, Brevibacterium stationis, Kurtha zopfil, Myrothecium verrucaris, Pseudomonas calcis, Pseudomonas dentrificans, Pseudomonas flourescens, Pseudomonas glathei, Phanerochaete chrysosporium, Streptmyces fradiae, Streptomyces cellulosae, Stretpomyces griseoflavus, Bacillus laterosporus, Bacillus bifidum, Bacillus laterosporus, and combinations thereof. [00274] Antispasmodic agents useful in combination with an LBP combination therapeutic method described herein can include anticholinergic agents. Exemplary anticholinergic agents for use in a method described herein can include, but are not limited to, oxybutynin (Ditropan), tolterodine (Detrol), flavoxate, fesoterodine, darifenacin, trospium, solifenacin, propantheline, duloxetine, dicyclomine, phenylpropanolamine, and hyoscyamine. In particular embodiments, the antispasmodic agent can be oxybutynin or a pharmaceutically acceptable salt thereof. For example, oxybutynin salts include acetate, bitartrate, citrate, edetate, edisylate, estolate, esylate, fumarate, gluceptate, gluconate, glutamate, hydrobromide, hydrochloride, lactate, malate, maleate, mandelate, mesylate, methylnitrate, mucate, napsylate, nitrate, pamoate, pantothenate, phosphate, salicylate, stearate, succinate, sulfate, tannate and tartrate. [00275] In some embodiments, the antispasmodic agent can include a beta-3 adrenergic agonist. Exemplary beta-3 adrenergic receptor agonists can include mirabegron (Myrbetriq) and vibegron. [00276] Antimicrobial agents useful in addition to an LBP combination therapeutic method described herein can include antibiotics, antiseptics, antivirals, antifungals, antiparasitics, and combinations thereof. Antimicrobials typically kill microorganisms and/or prevent their growth by targeting key steps in cellular metabolism such as the synthesis of biological macromolecules, the activity of cellular enzymes, or cellular structures, such as the cell wall and cell membranes. [00277] In particular embodiments, the antimicrobial agent for use in addition to an LBP combination therapeutic can include one or more antibiotics. The antibiotic agent for use in a combination therapy for the treatment or prevention of urobiome dysbiosis described herein can include any antibiotic effectively used for treating uropathogenic related urinary tract symptoms and/or urinary tract infections. In some embodiments, the antibiotic is selected from the group consisting of gentamicin, ampicillin, tobramycin, neomycin, polymyxin, amoxicillin, amoxicillin/clavulanate, ceftriaxone, cephalexin, cefpodoxime, cefdinir, cefadroxil, ciprofloxacin, fosfomycin, levofloxacin, nitrofurantoin, trimethoprim/sulfamethoxazole, and combinations thereof, such as trimethoprim/sulfamethoxazole and neomycin/polymyxin. In particular embodiments, the antibiotic agent is selected from the group consisting of gentamicin, tobramycin, colistin, neomycin, polymyxin and combinations thereof, such as neomycin/polymyxin. [00278] In some embodiments, the antibiotic for use in addition to an LBP combination therapeutic is gentamicin. Gentamicin is the most commonly studied intravesical antibiotic and when administered intravesicularly, it has been shown to be safe, tolerated, and effective for recurrent urinary tract infections (UTIs) in people with neurogenic lower urinary tract dysfunction (NLUTD) having little to no systemic absorption, nor nephro- or oto-toxicity (as with intravenous administration). [00279] In some embodiments, when administering an antibacterial agent in addition to the LBPs combination therapy described herein, the therapy dosing regimen can include a period of time (i.e., a wash out period) between administration of an antimicrobial agent and the administration of a dose of LBP. A wash out period can be used in order to allow colonization/recolonization of the LBP in the absence of the antibiotic, or a significant reduction in the amount of the antimicrobial agent remaining, in the urinary tract following antimicrobial agent treatment. In some embodiments, the wash out period is about 6 hours, about 12 hours, about 1 day, about 2 days, about 3 days or more. In other embodiments, a wash out period may not be required for the therapeutically effective treatment or prevention of UTI in a subject. [00280] In some embodiments, the one or more additional therapeutic agent administered to a subject in combination with the LBP combination therapy for the treatment or prevention of a UTI described herein can include a prebiotic fiber. A prebiotic fiber, or simply a “prebiotic”, can be selected from the group consisting of inulin, fructo- oligosaccharides (FOS), galactooligosaccharides (GOS), and combinations thereof. In an exemplary embodiment, the prebiotic fiber is inulin. [00281] In some embodiments, one of several weak organic acids (WOAs) can be administered in addition to an LBP combination therapy in order to inhibit the adhesion of uropathogenic bacteria in the lower urinary tract and promote growth of beneficial probiotic bacteria species. WOAs for use in a method described herein can include citric acid, acetic acid, quinic acid, and malic acid. In particular embodiments, the WOA is citric acid or acetic acid. In an exemplary embodiment, citric acid or acetic acid can be included in a pharmaceutically acceptable carrier used to formulate one or more Lactobacillus strains described herein for intravesical administration to the subject. [00282] In other embodiments, a steroid can be administered to a subject in addition to an LBP combination therapy described herein. In certain embodiments, the steroid is a corticosteroid. Exemplary corticosteroids can include, but are not limited to, alclometasone, amcinonide, beclometasone, betamethasone, budesonide, ciclesonide, clobetasol, clobetasone, clocortolone, cloprednol, cortivazol, deflazacort, deoxycorticosterone, desonide desoximetasone, dexamethasone, diflorasone, diflucortolone, difluprednate, fluclorolone, fludrocortisone, fludroxycortide, flumetasone, flunisolide, fluocinolone acetonide, fluocinonide, fluocortin, fluocortolone, fluorometholone, fluperolone, fluticasone, fluticasone propionate, fluprednidene, formocortal, halcinonide, halometasone, hydrocortisone aceponate, hydrocortisone buteprate, hydrocortisone butyrate, loteprednol, medrysone, meprednisone, methylprednisolone, methylprednisolone aceponate, mometasone furoate, paramethasone, prednicarbate, prednisone, prednisolone, prednylidene, rimexolone, tixocortol, triamcinolone, ulobetasol, and combinations thereof. [00283] In some embodiments, an NSAID can be administered to a subject in addition to an LBP combination therapy described herein. NSAIDs can refer to any of variety of drugs generally classified as non-steroidal anti-inflammatory drugs including, but not limited to, ibuprofen, flurbiprofen, diclofenac, salicylates (e.g. aspirin), COX2 inhibitors (e.g., celecoxib), indomethacin, piroxicam, naproxen, acetaminophen, and combinations thereof. [00284] Additional embodiments relate to a therapeutic kit to provide prevention and/or treatment of UTI in a subject in need thereof. The kit includes an effective dosage of an LBP, wherein the LBP includes Lacticaseibacillus rhamnosus and Lactobacillus crispatus as well as equipment necessary to perform self-administered LBP combination therapy. A kit may also include information and equipment necessary to prepare and/or formulate one or more effective doses of the combination of Lactobacillus probiotic agents for self-administration, e.g., via intravaginal, intraurethral, and/or intravesicular administration. [00285] A kit for the prevention and/or treatment of UTI in a subject typically includes packaging assembly having a container suitable for accommodating items in the kit. The kit may further include a UTI diagnostic test for screening a subject for UTI and the equipment necessary to perform a self-administered urine diagnostic test, such as a plurality of urine collection containers. A UTI diagnostic test can include equipment necessary to perform a self-administered UTI diagnostic test for the detection of a UTI in urine. The UTI diagnostic tests can also include a plurality of leukocyte esterase and nitrite rapid screening urinary test strips. [00286] The kit can also include information related to the treatment decision-making criteria for determining the likelihood of having a symptomatic UTI in a subject as described above that can be used to determine if a user is suitable for LBP combination therapy included in the kit. [00287] A kit for the prevention and/or treatment of UTI in a subject in accordance with embodiments described herein may also include information relating to LBP combination therapy, any additional therapeutics agents described herein for the treatment of a UTI included in the kit, and instructions on how to select and self-administer an LBP and/or additional therapeutic agents. In particular embodiment, the kit includes one or more doses of Lacticaseibacillus rhamnosus GG and Lactobacillus crispatus CTV-05 (LACTIN-V). [00288] The present invention is illustrated by the following examples. It is to be understood that the particular examples, materials, amounts, and procedures are to be interpreted broadly in accordance with the scope and spirit of the invention as set forth herein. EXAMPLES Example 1 [00289] The current clinical approach to diagnosis and treatment of UTI represents “harms associated with indiscriminate use of antibiotics [for presumed UTI] associated with lack of diagnostic clarity” (Brubaker, L et al. Front. Urol.3, (2023). Treatment of UTI and other lower urinary tract symptoms (LUTS) with intravesical instillation of various therapeutics is an accepted clinical option, yet these are typically recommended only as a last resort. For example, use of bladder washes with normal saline (and mixed with citric acid) is FDA approved for bladder catheter encrustation but is recommended only after repeated catheter clogging (often leading to emergency room visits and risk for kidney injury and/or autonomic dysreflexia). Similarly, intravesical instillation of therapeutic agents for UTI has been accepted clinical practice since the late 1980’s, however, many clinicians are unaware of this option and these methods are typically only recommended after multiple infections and exposures of the body and its microbiome to antimicrobials. [00290] Here, we describe targeted intravesical treatment of UTI and LUTS with antibiotics coupled with a live biotherapeutic product (LBP). Intravesical antibiotics will locally reduce uropathogen burden and activity, while the LBP will restore and reconstitute a healthy urobiome that will protect against uropathogens and prevent future UTI. This approach will be superior to standard of care in effectiveness and safety at the individual level. It also will be superior at the societal level, as it limits overall exposure to antibiotics, thus limiting antibiotic resistance. Given the urgent global public health threat of antimicrobial resistance, this is a critical shift toward antibiotic stewardship, and away from the current paradigm of searching for stronger antibiotics for stronger superbugs. As individuals with spinal cord injury or disorder (SCI/D) may already manage their bladders with catheters (indwelling, IDC or intermittent, IC), intravesical instillation should not be considered a "last resort." [00291] In addition, a first-in-human study of coupled antibiotic-LBP treatment for UTI among people with NLUTD due to SCI/D is performed. Gentamicin is the antibiotic with the strongest evidence base for intravesical instillation among people with SCI/D and has been effective in preventing recurrent UTI. We have shown that intravesical Lacticaseibacillus (formerly Lactobacillus) rhamnosus LGG (LGG), given as 1-2 doses, is a safe and well tolerated LBP that reduces urinary symptoms and alters urobiome diversity. [00292] Optimal dosing and timing of coupled intravesical instillation of gentamicin and LGG (termed “gent-LGG”) may be determined among people with NLUTD due to SCI/D. Our preliminary data (see below) supports the hypothesis that successful colonization of the bladder with LGG reduces urobiome dysbiosis and results in resistance to UTI and other LUTS. [00293] Dosing of gentamicin is informed by clinical evidence from 7 studies with dosing ranging from daily to 4/d. Timing of the coupled intravesical treatments is determined through in vitro testing, with results replicated, and studied for feasibility, in males and females in a mouse model. The definition of "successful colonization of the bladder with LGG" is confirmed and replicated in males and females with SCI/D. Preliminary Data [00294] Despite decades of research, understanding of UTI remains limited. Significant strides have been made in countering widely accepted myths. The new paradigm: the urinary tract is not sterile. [00295] Our preliminary results demonstrate the deficits in both diagnosis and treatment ^^^^^^%^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ health. The current UTI diagnosis, treatment, and antibiotic resistance paradigms do not account for the urobiome - the newly discovered communities of microbes (bacteria, archaea, protists, fungi, and viruses) that inhabit the urinary bladder. Traditional clinical care algorithms are based on the “urine is sterile” dogma, a belief based primarily on the use of standard urine culture (SUC) methods commonly used by clinical microbiology laboratories and optimized to detect E. coli. High throughput 16S rRNA gene sequencing and our novel enhanced urine culture (metaculturomic) protocol (Expanded Quantitative Urine Culture [EQUC]) reveal bacterial DNA and live bacteria, respectively, in catheterized (bladder) urine deemed culture-negative by SUC (for details, see below). These studies have revealed associations between the bacterial species of the female urobiome and post-instrumentation and post-operative UTI, urge urinary incontinence (UUI), and response to overactive bladder treatment. Some Lactobacillus species are associated with a lack of symptoms and protection against post-instrumentation UTI. These results strongly support the proposition that certain bacterial species of the human urobiome have protective capabilities, and that imbalance (dysbiosis) can result in disorders, such as UTI. [00296] Neurogenic bladder is associated with dysbiotic bladder urobiomes. We were the first to compare the urobiomes of people with SCI/D and NLUTD to those of neurologically intact controls. This work verified the existence of the urobiome, showing that most control female urobiomes are predominated by Lactobacillus and some control male urobiomes contain Lactobacillus, but most do not (Fig.1). We also showed that NLUTD urobiomes are dysbiotic, depleted in beneficial bacteria as most NLUTD females lacked or had reduced Lactobacillus levels, while most NLUTD males lacked the Streptococcus and/or Corynebacterium that was commonly observed in control males. These results show that NLUTD bladders of most females and at least some males could be colonized by LGG, and that LGG in the urobiome could improve urinary symptoms. Live Biotherapeutic Products (LBPs) are a promising treatment option [00297] LBPs are microbiome-modulating therapies (such as probiotics) that may promote health by restoring homeostasis to a dysbiotic microbiome. As an intervention, LBPs can correct urobiome dysbiosis associated with UTIs and other LUTS. While the exact role of LBPs in urobiome homeostasis remains unknown, there are several hypothesized mechanisms, including competition with pathogens for nutrients and attachment sites, biofilm disruption, production of antimicrobial factors, immunomodulation, and regulation of gene expression. Given their predominance in the urinary and vaginal microbiomes of healthy women, lactobacilli, including LGG, have been the focus of much work on probiotics and LBPs. Early in vitro work showed that lactobacilli presence decreased uropathogen adherence to urothelial cells, while in vivo studies showed specific species of lactobacilli inhibit growth of uropathogenic E. coli (UPEC). Also, certain species of lactobacilli produce antimicrobial peptides (AMP), proteins that function within the innate immune system. Various AMPs are upregulated in the genitourinary tract in the setting of UTI, and gene editing studies show that the lack of AMPs is associated with increased uropathogen presence. However, AMPs require activation by proteases, and proteases produced by the urothelium are dependent on an acidic pH. Given that lactobacilli species produce acid, thereby lowering environmental pH, it is likely that AMP activity within the genitourinary system is at least partially dependent on sufficient presence of lactobacilli within the urobiome. These data suggest that lactobacilli species play a role in protecting the genitourinary tract from UTI. Of the LBPs considered for LUTS and UTI, LGG is the best studied. LGG is safe and well tolerated when instilled into NLUTD bladders. [00298] In our 18-month first-in-human phase I/II clinical trial of intravesical LGG in response to urinary symptoms (cloudy and/or more foul-smelling urine), we found that instilled LGG was safe and well tolerated. Specifically, 13 adverse events (AEs) and 46 serious AEs (SAEs) occurred over the 18-^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ independent Data and Safety Monitoring Board (DSMB) to be ‘definitely’, ‘probably’, or ‘possibly’ related to the study drug. Six (46.2%) of the AEs and 23.9% (11) of SAEs occurring at any time point after LGG use included irritation after instilling (1), UTI (1), emotional discomfort due to a UTI (1), UTI and kidney infection (2), and migraine (1). Of the 11 SAEs, 7/11 were considered by the DSMB to be 'definitely unrelated to the study drug' while 4 were considered to be ‘unlikely to be related’ to the study drug, including bladder infection (1), prostate infection (1), severe kidney infection (1), coughing (1) and urinary symptoms (1). There were no Lactobacillus UTIs. [00299] LGG disrupts the dysbiotic NLUTD urobiome. In a first-in-human trial of self- instillation with 1-2 doses of intravesical LGG vs. normal saline mixture, instillation of LGG resulted in significant changes in urobiome composition with reduced abundance of the uropathogenic genera Escherichia/Shigella and Aerococcus, but no significant change in other uropathogens (Klebsiella, Proteus, Pluralibacter, and Enterococcus) or commensals (Lactobacillus, Veillonella, Staphylococcus, Streptococcus). The sample size was too small to ^^^^^^^^^^%^^^^^^^^^^^^^%^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^%^^%^^^^^ future clinical application to positively impact NLUTD-related urobiome dysbiosis and other LUTS. The Mouse Urobiome. [00300] The current mouse models of UTI were developed decades before the discovery of the urobiome. Since a fundamental assumption is wrong - that the mouse bladder is sterile - existing data interpretation is likely skewed. It is believed that the complexity of the mouse urobiome is one reason why current mouse models of UTI require instillation of massive numbers of uropathogens (10^7-8 colony forming units/mL) - orders of magnitude greater than what likely naturally initiates a UTI or other urinary tract disorder. Fig.2 reveals a mouse urobiome consisting primarily of Staphylococcus xylosus, S. urealyticus, S. capitis, Escherichia, Enterococcus faecalis, Lactobacillus johnsonii, Ligilactobacillus apodeme, Pseudomonas migulae, Mammaliicoccus lentus, Cutibacterium acnes, Alkalihalobacillus, Anaerobacillus, and Turicibacter. These data are critical to the development of translatable mouse models where results can directly translate into clinical care. This work is also an important step towards understanding and overcoming colonization resistance in our pursuit of effective treatments for UTI and other LUTS. [00301] Along with the immune response, the mouse urobiome also may contribute to the clearance of instilled uropathogens within hours by some mouse lines, precluding their use in UTI research. Despite decades of research on mouse models of UTI, there are currently no published data describing the mouse urobiome. Since the native mouse urobiome likely influences the ability of invading microbes (e.g., UPEC) to cause UTI, and to pursue our proposed goal of ensuring LGG colonization in male and female mice, we have begun to describe the normal mouse urobiome, starting with wild type (C57BL/6) mice, commonly used for UTI studies. Human-derived Lactobacillus sp. can colonize the mouse bladder [00302] We also have focused on colonizing the mouse bladder with human-derived lactobacilli. First, we optimized an anaerobic culturing system specifically for Lactobacillus to ensure that the instilled strain had an optimal chance for bladder colonization. After a subsequent time-course experiment, we discovered that 10 minutes of dwell time in the bladder ensured Lactobacillus colonization, and that dwell times beyond 10 minutes did not improve colonization rates. Colonization resistance and the urobiome [00303] A major consequence of our work is the realization that efforts to alter the urobiome for the purpose of research in mice or therapy in humans must consider colonization resistance, the inhibition of colonization of an incoming microbe by those that are already colonizing a niche. Therefore, we believe that the pre-existing host urobiome can directly affect the ability of another bacterium to colonize. Building on our previous work, we now study the transformational change to the UTI treatment paradigm that addresses existing misconceptions and builds on current evidence around the urobiome. Objectives [00304] Here we focus on the population of people with SCI and NLUTD who manage their bladders with intermittent catheterization (IC). The objectives of this research among this population will determine the optimal (1) timing and (2) dosing of intravesical gentamicin and LGG administration to inhibit uropathogens and promote colonization of the ^^^^^^^^^^^^^^^^^^^^^^^^^^7(9^^^^^^^^^^^^^^ ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ therapy. Goals [00305] 1. Determine requirements for successful in vitro re-colonization after gent- LGG combination treatment. [00306] 2. Determine the optimal period between gent and LGG administration to optimize bladder re-colonization for males and females in vivo (mouse model of SCI+NLUTD). [00307] 3. Pilot Clinical Trial. Determine in men and in women with SCI/D and NLUTD: whether timing and dosing ( Goal 1& 2) affect success of re-^^^^^^*^^^^^^^^^^^^^^ ^^^^^^^^^^^^^^^^^^*^^^^^^^^^^^^/^^2-^^^^^!0^^^^^^^^^^^^^^^^^^8^^^^^^ 6:)86:^^^^^^^^^7"#8^ burden) of coupled intravesical gent-LGG. Design And Methods 1. Determine Requirements For Successful In Vitro Re-Colonization After Gent-LGG Combination Treatment Rationale [00308] Successful colonization of a protective microbe (e.g., LGG) first requires elimination of native microbes that compete with an introduced LBP. Colonization resistance refers to a set of mechanisms by which native pre-existing microbiota resist colonization by invading microbes. For example, introduction of LBP E. coli into the mouse gut requires pre- treatment with streptomycin to kill pre-existing competitors. Although intravesicular LGG instillation decreased some pathogenic genera (Escherichia/Shigella and Aerococcus) and reduced urinary symptom burden for people with SCI/D, it did not decrease many other uropathogenic genera and the results were only observed in some participants, not in all. These results reflect successful colonization of LGG in some participants and may suggest colonization resistance in others. More robust colonization should result in improved patient outcomes. General Strategy [00309] To identify species that can impede LGG colonization, we will assess LGG's ability to thrive in the presence of native urinary species. To identify antibiotics that inhibit growth of putative competitors without harming LGG, antibiotic susceptibility profiles of LGG and its competitors are determined. Interactions between species can influence ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^7;;^^^^^^-cultured with species identified as the most inhibitory are assessed. Finally, it is determined if the entire ecosystem performs as anticipated in the context of a human bladder organoid system. Success is defined as LGG colonization when organoid systems are co-inoculated with both known competitors and antibiotic. Thus, tests are performed first in vitro and then in the context of human bladder organoids. Feasibility/Preliminary Data [00310] A large pre-existing collection of human urinary strains. We possess a biorepository of >13,000 urinary bacterial strains that span the entire phylogenetic spectrum, primarily from the phyla Actinomycetota (formerly Actinobacteria), Bacteriodota (Bacteroidetes), Bacillota (Firmicutes), and Pseudomonadota (Proteobacteria). L. rhamnosus is a member of the phylum Bacillota, which contains Lactic Acid-producing Bacteria (LAB). LAB includes L. rhamnosus and other urinary species in the families Aerococcaceae, Enterococcaceae, Streptococcaceae, and Lactobacillaceae. All are phylogenetically related, and all metabolize complex polysaccharides (e.g., glycogen) to ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^+^^^^^^^^^^^^^^7;;^^^^^^^*^^^^^^ Newly designed assay for fastidious bacterial species [00311] Some bacterial isolates from the human urobiome have been extensively studied ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^+^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ fastidious, i.e., difficult to grow in vitro. We have established a method to determine the antibiotic resistance of previously undescribed bacteria, such as those in the families Aerococcaceae and Lactobacillaceae, which have a difficult time growing in the standard Mueller Hinton Broth. This method uses a serum-based medium (NYCIII ATCC Medium#1685) and a high throughput broth dilution method. We have shown that NYCIII broth dilution determines antibiotic resistance of the usual suspects in urinary microbiome pathology (i.e., Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus aureus), comparable to Clinical and Laboratory Standards Institute (CLSI) standards. We then used this method to obtain antibiotic susceptibility profiles on fastidious and slow growing urinary species with no CLSI guidelines (e.g., Aerococcus urinae, Lactobacillus crispatus, and Streptococcus anginosus). Antimicrobial resistance by genome mining and phenotyping. [00312] The spread of antibiotic resistance genes (ARGs) is one of the primary drivers of resistance in bacterial communities, especially in the urobiome. When we sequence the genomes of our bladder isolates, we utilize databases such as the Comprehensive Antibiotic Resistance Database (CARD) and VRprofile to predict resistance phenotypes. Combining these tools, we have developed our own bioinformatic algorithms to analyze our thousands of isolates and compare our predictions to antibiotic susceptibility tests. In a 1st demonstration, we examined 28 Aerococcus urinae genomes for resistance to macrolides and tetracycline. After testing these strains against the actual antibiotics, our analysis successfully predicted 85.7% of strain resistance phenotypes. Our 2nd study included an expanded set of 54 genomes that consisted of members from the orders Actinomycetales and Lactobacillales. Assaying for 17 different ARG genes, we successfully predicted 78% of strain resistance phenotypes. Current studies include testing 100s of urinary strain genomes, comparing pre- COVID and post-COVID bladder isolate resistance profiles. Preparing for this study, we subjected 392 genomes from the LAB families Aerococcaceae, Enterococcaceae, Streptococcaceae, and Lactobacillaceae to CARD and VRprofile, which predicted most are resistant to aminoglycosides and tetracycline with many fewer to chloramphenicol, colistin, ^^^^^^<^^^^^^^^^^^;-20^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^.^ antibiotic classes, including gentamicin. ^{Human bladder organoid model}^^ [00313] Mouse models and monolayers derived from cancer cell lines are commonly used in UTI research. However, these models often differ in terms of structures, genetics, innate immune response, and functionality compared to a human bladder. These differences prevent accurate translation of UTI-related research from these models to humans. An alternative is a human urine-dependent bladder organoid. The polarized, multilayer urothelial organoids are produced from spontaneously immortalized bladder progenitor cells, which undergo differentiation on addition of calcium-rich media. Further differentiation requires filter-sterilized human urine. Urine prompts differentiation of the bottom layer into basal cells, middle layers into intermediate cells, and the apical layer into umbrella cells. These umbrella cells shed in response to uropathogenic invasion and express uroplakin III, which is exclusively expressed by umbrella cells and has been shown to be crucial for E. coli bladder colonization. Thus, this model closely mimics normal bladder physiology, is stable, reproducible, and offers excellent translatability for UTI research. Images of this human bladder organoid model system are illustrated in Fig.3. Experimental Design Step 1 – Identify LGG competitors [00314] As noted, the most likely competitors of LGG in the NLUTD bladder are members of the families Aerococcaceae, Enterococcaceae, Streptococcaceae, and Lactobacillaceae. All are LAB and all are present to some degree in NLUTD bladders. LGG is known to be beneficial, but the others are uropathogens (e.g., Aerococcus urinae, Enterococcus faecalis, Streptococcus anginosus). Inhibiting these prior to instillation with LGG would reduce likelihood of colonization resistance and improve LGG colonization. A similar situation exists for the wild-type mouse urobiome, where E. faecalis (uropathogenic) is relatively common. To identify those LAB that compete with LGG, we will use our Co- Culture Duet System. This high throughput system allows us to independently monitor the growth of multiple pairs of distinct bacterial populations. Due to a porous membrane barrier between wells, study populations share the same environment without physical interaction. Thus, if one population secretes/excretes a molecule that inhibits or enhances growth of the other, we can detect it in real-time. Each pair includes LGG and a pre-existing urinary isolate of a putative competitor species. For reproducibility, multiple isolates of the same species will be assessed. Step 2 – Determine the antibiotic susceptibility profiles for LGG and competitors [00315] We have sequenced and deposited in the NCBI database the genomes of ~1300 isolates, including many of the LAB bacteria. These genomes will be assessed using CARD and VRprofile to predict ARGs. Predicted resistances are verified via susceptibility testing in the high throughput broth dilution method described above. Briefly, this high-throughput phenotype assay uses a 96-well microplate setup that assesses bacterial growth in the presence of a range of antibiotic concentrations. As described, we utilize NYCIII as the growth medium for fastidious facultative anaerobic bacteria that normally cannot grow on standard MHB medium. Since we place our microplate spectrophotometers in controlled- environment chambers, we can adjust gas and temperature conditions to meet the requirements for these fastidious bladder microbes. This is especially critical for assaying obligate anaerobic bacteria. As such, we can obtain minimum inhibitory concentrations (MICs) for a plethora of antibiotics. As interactions between bacteria can occur, we then obtain MICs when LGG and potential competitors are co-cultured in the previously described Duet System. Step 3 – Test relationships in a bladder organoid system [00316] To establish organoids, we seed freshly passaged HBLAK bladder progenitor cells (CellNTec) onto the apical surface of a 12-well transwell membrane, and incubate for 72 hours in low calcium, low magnesium media to allow attachment and proliferation. Once confluent, we change the media to high calcium, high magnesium differentiation media and incubate for 24-48 hours. Once cells form a monolayer with typical bladder cell morphology, we replace media of the internal well with filter-sterilized human urine. Direct contact with the apical layer of cells allows for polarization. After 14-21 days, the cells develop into a multilayer consisting of 4-5 complete cell layers. The layer in contact with the transwell membrane and the middle layers take on basal cell and intermediate bladder cell morphologies, respectively. The apical-most layer, in direct contact with urine, differentiates into umbrella cells that express uroplakin III and a thick GAG-layer. The “mature” bladder organoid is confirmed by confocal microscopy. To assess the ability of LGG to colonize organoids, we grow it under suitable conditions to a desired OD, then wash in PBS before dilution to the desired MOI in filter-sterilized human urine. 400 µL aliquots of LGG is added to the apical side of mature bladder organoids. After a 2-hour incubation, the apical media is removed and replaced with fresh differentiation media alone (control) or differentiation media with gentamicin. After another 2-hour incubation, organoids are lysed with 0.2% triton and samples plated onto appropriate agar to quantify organoid associated (attached and intracellular) and organoid invasive (intracellular only) bacterial CFUs. One transwell- membrane from each infection condition is stained for confocal microscopy, allowing for visual confirmation of bacterial attachment to and intracellular invasion of the organoid. Confocal imaging is used to distinguish between tissue penetration, with bacteria present in deep tissue layers external to bladder cells, and true intracellular invasion, where bacteria are clustered in bladder cell cytoplasm. We assess 1) if LGG is gentamicin sensitive when present with urothelial cells and 2) if it can invade the urothelium and thus be protected from gentamicin. To test how LGG behaves when confronted with a competitor, the protocol is altered to 1st inoculate organoids with a competitor, allow attachment/invasion, add differentiation medium with or without gentamicin, and incubate for 2 hours. Instead of immediate lysis, the media is replaced with fresh media without gentamicin, inoculate with LGG, incubate for another 2 hours, then lyse and assess attachment/invasion. Anticipated outcomes, alternative approaches, and advances to clinical and research efforts [00317] For step 1, we anticipate no problems as we know the growth conditions for all the bacterial genera in question and the Duet System is established in our lab. The expected outcome is a list of species that inhibit or enhance LGG growth. In preparation for step 2, we analyzed >1200 genomes (including LGG, other Lactobacillaceae, and potential LAB competitors), and found no gene specifically associated with gentamicin resistance. However, some resistance mechanisms are not specific (e.g., multidrug efflux pumps). Thus, while we have some reason to believe that gentamicin will reduce bacterial load prior to LGG instillation, step 2 is necessary, as we must directly expose likely competitors to gentamicin. If a competitor is found to be resistant to gentamicin, a 2nd antibiotic can be added. For step 3, we anticipate no problems exposing the organoids to LGG or its competitors alone, as the protocol is well established. In contrast, optimization of the establishment of organoids pre- colonized with competitors is expected. [00318] Successful completion of this aim informs aspects of both Goal 2 and Goal 3 and provides foundational knowledge for instillation of LBPs in human bladders. It confirms use of a novel approach to obtain antibiotic susceptibility profiles for fastidious microbes – useful for clinical microbiology laboratories. It also establishes an organoid model for determining if antibiotics actually work on bacteria in the presence of urothelial cells. 2. Determine the optimal period between gentamicin and LGG administration to optimize bladder colonization [00319] Simultaneous to Goal 1, an animal model is used to determine if LGG can be administered concurrently with gentamicin, or if an interval washout period is necessary to optimize LGG colonization in the bladder. The results of this aim inform the timing of LGG with regard to gentamicin in Goal 3. Mouse model of SCI [00320] A spinal cord transection model in 9-week-old male and female C57BL/6 mice is used. Although spinal cord transection is not the most common etiology of SCI in people, it reliably results in NLUTD, the phenotype of interest for NLUTD urobiome work. Mice are anesthetized, and the cord transected between T8 and T9. All mice are given both ampicillin and ketoprofen per st^^^^^^^^^^^^^^^^^^^^^^^^^^%^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^8=$^ ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ (specifically potential effects of ketoprofen, a non-steroidal anti-inflammatory drug) are involved in development of dysbiosis in humans with NLUTD, these also can be incorporated into the animal model. Sham animals undergo the same process and treatments, but without the actual cord transection. Confirm urobiome of mice with SCI [00321] We anticipate, and will confirm, that the urobiome of mice with SCI reflect that of humans and consist predominantly of Gram-negative uropathogens. Confirming the underlying urobiome of mice with SCI prior to initiating instillation of gentamicin and LGG is critical, given the need to identify urobiome species in mice with SCI that offer colonization resistance. As mentioned above, the wild-type mouse urobiome is often colonized by the uropathogen E. faecalis, which could confer colonization resistance. To confirm this, SCI is induced in C57BL/6 mice (1:1 female:male) and create sham mice (1:1 female:male) as controls. After inducing SCI (or sham) in mice (which requires antibiotic administration per standard of care, noted above), we wait a period of time before assessing the urobiome. To determine the necessary amount of time between completion of peri- operative antibiotics and urine collection for urobiome analysis, qPCR is used on mouse urine (collected weekly) with universal 16S primers to determine total bacterial burden as a proxy measure of urobiome reconstitution. Ultrasound-guided suprapubic aspiration is used to collect all urine samples from mice to minimize contamination risk (Fig.4). We acknowledge that the urobiome may be somewhat dynamic, and thus composition may change while total bacterial burden is stable. However, in terms of time and cost, the most reasonable measure for stability is bacterial burden, which we will define as the total bacterial burden stable for 3 serial, weekly, measurements (as assessed by qPCR). Once the urobiome is established as stable, urine samples are collected from each mouse to analyze the baseline urobiome, as we did with wild-type mice (see preliminary data). We qualitatively compare the stable urobiome patterns in male and female sham mice to those with SCI to confirm observations about the development of dysbiosis due to post-operative treatment with antibiotic rather than specific aspects of induced NLUTD. Urine is preserved with AssayAssure, a DNA-stabilizing reagent, and frozen at -80°C prior to sequencing being performed. [00322] This data improves understanding of the origins of dysbiosis observed in NLUTD and demonstrates the translation potential of this mouse NLUTD model for humans. Also, 16S sequences are used from the baseline urine samples to design primers specific for LGG and relevant uropathogens identified. Determine the optimal washout period between intravesical gentamicin and LGG [00323] The pharmacokinetics of gentamicin in vitro will not match those in vivo^^^^^^^^^^ mammalian model is needed to determine the proper interval between intravesical gentamicin and LGG administration based on the in vitro results from SA1. Urethral catheterization is used to instill substances into the bladders of male mice. SCI in 9-week-old C57BL/6 mice are induced as described. Intravesical gentamicin instillations begin after the urobiome has reached stability as determined by qPCR (as described above). Prior to the 1st gentamicin instillation, a baseline urine sample is collected. Both gentamicin and LGG are instilled using transurethral catheterization. A syringe pump is used to standardize instillation time of 1 minute and not instill more than 50 microliters of either gentamicin or LGG as larger volumes can cause reflux to the kidneys. Supported by the literature, intravesical gentamicin is administered (dwell time 1 hour) to all mice twice a day for 5 days using a dose of 4 mg/ml. Animals are split into the following groups: simultaneous (LGG to be administered simultaneously with gentamicin for the final 24 (low dose) or 48 (high dose) hours of the gentamicin 5-^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^^^^^^^^^^^^^^7;G to be administered 12 hours ^^^^^^^^^^^^^^^^%^^^^^^^^^^^^^^^^^^^^^^^^%^^^^^^^^^^ ^^^^^^^^^^^^^^7;;^^^^^^^^^^^^^^^^^^^^!-^ hours after the final gentamicin dose). The dose of LGG is 10⁹ colony-forming units, which was sufficient to induce transient bladder colonization in wildtype mice previously. Either 2 doses of LGG in 24 hours ("low dose") or 4 doses in 48 hours ("high dose"), as informed by ongoing studies in humans. This 3 (timing) x 2 (dose) factorial requires 10 female and 10 male mice per group (total N=120). To accommodate potential loss of 20% of our samples, 2 extra mice are included per group, thus, the final sample size at 144. Five male and five female mice are also included in the sham condition (no instillations). [00324] The outcome of this goal informs the timing of LGG after gent to be used in SA3. The dosing of both gentamicin and LGG are fixed but the timing is unknown. To determine which of our three timing options results in the highest and most consistent rates of successful re-colonization with LGG, “successful bladder colonization” is defined by L. rhamnosus to be an increase of ≥30% in its abundance (amplicon sequence variants [ASV] by qPCR) compared to the baseline value obtained immediately prior to the first dose of gentamicin. This increase will be relative to the baseline value unless the baseline sample had zero L. rhamnosus, in which case the increase will be absolute. Each mouse is determined if they did/did not meet this definition of success and summarize rates of success at 24 h, and 7, 14 and 28 days after final LGG instillation. A secondary indicator of success is based on the uropathogen to Lactobacillus (U/L ratio). For this exploratory indicator, we define “successful bladder colonization” as an increase in the U/L ratio of at least 25% from baseline and assess for success under each definition from the urine of mice at pre-gentamicin and at 7, 14 and 28 days post the final instillation. Statistical analysis [00325] Analysis will use an intent-to-treat approach, with all mice analyzed in assigned ^^^^^^^^^^%^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^%^^^^^^^^^^^^^^^^^^^^^^8=$^ and sham in effects on the baseline urobiome of the post-operative antibiotic protocol, within ^^^^^^>^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^^^^^^^^^^^ be tested. We use a two 1-way ANOVAs prior to initiating gent-LGG instillations to determine if differences exist in age and weight across the 6 (3 x 2) dose-timing groups, within sex. Main analyses (?2 on success rates) are be performed separately for each definition of success and separately by sex. Success rates are estimated under the 2 definitions at 5 timepoints relative to baseline (Table 1) for samples 2, 3, 4, 5, and 6, yielding a total of 2 (definitions of success) x 2 (sex) x 5 (success rate estimates) ?2 across 6 dose-timing groups. Sample sizes are planned with 20% extra to accommodate loss during intervention and 28-day follow up, so no imputation is performed in the instance of missing data. The latest versions of SPSS (29 or above) and R (4.3.1 or above) with be used for data management and statistical analysis. [00326] The number of males and females in each of the six dose-timing groups who demonstrate 30% increase in total abundance (definition of "successful colonization") are computed based on comparisons of samples 2-6 to sample 1 (baseline). Mice who exhibit <30% change in Lactobacillaceae species abundance are counted as a “colonization failure” (definition 1). Similarly, success and failure rates are determined based on 25% change in U/L ratio (definition 2). For each definition of "success", and separately for males and females, we estimate proportions of successes in each dose x timing group (n=6). A statistically significant difference in success rates is not anticipated based on timing of LGG after gentamicin given the sample sizes. Instead, we determine if one timing paradigm results ^^^^^%^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

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Given the highly dynamic nature of the urobiome ecosystem, we treat the success rate based on qPCR at each timepoint as independent, so uncorrected alpha of 0.05 is allocated to each analysis. Individual results are not treated as "the answer" but rather as "a signal". The patterns of "wins" are explored by dose- timing and definition of "successful colonization". Given that there are 10 mice per group, there is adequate power for each ^² analysis. The data is leveraged by combining the patterns of "wins" to determine which timing option is most likely to optimize the pilot clinical trial in SA3. Anticipated problems and alternative approaches [00328] A potential problem is that the urobiome of mice with SCI may not mirror the urobiome of humans with SCI. If so, efficacy of gentamicin is assessed against the most common taxa in the urobiome of mice with SCI. If gentamicin has activity against these microbes, we proceed with gentamicin. If not, an antibiotic is identified with activity against these microbes and directly compare each antibiotic’s effect in establishing LGG colonization. We also may have difficulty ensuring the survival of enough mice with SCI for the required period. Thus, a conservative is used to estimate the number of mice to account for 20% mortality. Although unexpected, should we have difficulty with the mouse SCI model, we transition to a genetic model of myopathic bladder, the Chrm3^-/- mouse. The Chrm3^-/- mouse exhibits impaired detrusor contractility in vitro, with similar cystometric pressures to control mice. We have data showing that the urothelium and associated GAG layer of Chrm3^-/- mice is similar to that in SCI mice, further supporting this model as an alternative. Prior to using the Chrm3^-/- mice, we would analyze their urobiome versus controls to assess if the Chrm3^-/- urobiome replicates that of humans with SCI. [00329] Lastly, mouse models are critical to inform clinical research but, to date, there is no proper mouse model for urobiome research. We have overcome hurdles of mouse urobiome research to develop a model for future in vitro work and to determine if separate models are required for male and female mice. This work will be the 1^st use of our improved model to be ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ preclinical urobiome studies. 3. Determine in men and in women with SCI/D and NLUTD: whether timing and dosing (see Goals 1&2) affect success of re-^^^^^^*^^^^^^^^^^^^^^^^^^^^^^^^^^^^*^^^^^^^^^^^^/^^2-^^^^^!0^^^^^^ ^^^^^^^^^^^^^^^^^^^ 6:)86:^^^^^^^^^7"#8^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^%^^^-LGG. We define successful re-colonization with LGG to be at least 30% increase in the abundance of Lactobacillaceae given each individual’s baseline abundance. [00330] Here we describe a new treatment paradigm for UTI among men and women with NLUTD due to SCI/D. Instead of oral or intravenous antibiotics guided by SUC and without consideration for reconstitution of the urobiome after antibiotics are complete, we propose targeted intravesical antibiotics coupled with an intravesical live biotherapeutic product (LBP) for urobiome restoration. This shift is consistent with scientific evidence, as well as the CDC's concerns about MDROs and general considerations of antimicrobial stewardship. Because it has been shown that gentamicin successfully reduces LUTS and uropathogens when administered intravesically, and that 1-2 doses of intravesical L. rhamnosus (LGG^) is safe and well tolerated, reduces urinary symptoms, and alters urobiome, we propose these therapeutics be coupled. Here, we seek to determine optimal timing of the gent-LBP transition of therapy (can they be administered at the same time or is a washout period required?) and number of doses of LGG to assess if and to what extent L. rhamnosus successfully colonizes the pre-treated bladder in men and women. Design [00331] An overview of how the randomized clinical trial is conducted is illustrated as shown in Fig.5. Target Enrollment [00332] N=48 participants (N=24 men and N=24 women). Setting [00333] Washington, DC and Pittsburgh, PA. Inclusion Criteria [00334] 2^^^%^@20^^^^^^^^!^^8=$)A^^^^^^^^^^.-months ^^^^^^^^^^^^^B7"#A^^-^^^^^^^*^^%^ ^^^^^^^^^^^^^^^^^^^^^^*^^^^^^ $=^^^^^^^^^^^^^^^^^^%^^^^^^^^^^^^^^^%^^^^^^"#$^ ^^^"8CB(-IC A ^^^^(2^^^^^^^^^^^^^^^^^^^^%^^^^^^^^^"#$^^^^^^^^^!-^^^^^^^^^^^^^^^^^^^^^^^^^%^^^^^^^^^^^^^^^.^^ community dwelling. Exclusion Criteria [00335] 1) known genitourinary pathology beyond NLUTD (i.e., vesicoureteral reflux, ^^^^^^^^^^^+^^^^^^^^^^^^^^^^^^^^^!^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^%^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^-^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^!^ ^^^+^^^.^^^^^^^^^^%^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^%^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ 7) participation in another study by which results would be confounded. Individuals who endorse both A and B1 USQNB-IC symptoms (suggestive of a UTI) can remain potentially randomizable for a period of one month. Those who cannot achieve zero A and B1 symptoms on the USQNB- IC during a 14-day period are excluded. Controls [00336] Each participant serves as their own control to determine successful colonization with LGG. Recruitment [00337] Based on previous results, we conservatively estimate 20% dropout. To achieve our target of 10 per group, with 20% dropout we randomize 12 per group. Thus, recruit 24 men and 24 women (48 total). We have successfully achieved this level of recruitment and retention in prior, longer (18 months) studies. Data Collection [00338] All data from subjects are recorded using electronic case report forms (eCRFs) in the Research Electronic Data Capture (REDCap) data management system. Validation is employed for all eCRFs to minimize out of range and missing values, and further quality control is ensured by the data team. Levels of missingness, variable distributions, and excessive outliers are examined throughout data collection for quality assurance as well as prior to statistical modeling. Urine samples are collected and preserved/frozen by participants and shipped to our lab for analysis by 16S sequencing and qPCR analysis. 16S and qPCR results are entered into csv files and linked to REDCap. Initial Assessment [00339] Participants complete the International SCI Lower Urinary Tract Function Basic Data Set [NINDS CDE], and NINDS SCI CDE (medical history, prior/concomitant medications [per NINDS CDE]. Randomization [00340] Men and women in the two regions (DC, Pittsburgh) are randomized (within sex) 1:1 to either receive “Low” or “High” dose LGG (to be prepared a priori by the Co-I and senior biostatistician (RET)). Intervention Training [00341] We have completed training manuals on instillation of intravesical LGG developed through our PCORI-supported pilot safety trial and CDMRP-supported LGG dosing trial. We will add preparation and instillation of intravesical gentamicin to the training information. Two individual training manuals will be developed for use by males and females in the low or high gent-LGG groups with number of instillations, time intervals between doses, and urine sampling specified for each group. Participants are given a manual (hard copy or electronic, per subject preference) and complete a 1-on-1 training session with our SCI/D person with lived experience (PLEX) consultant. Intervention Materials [00342] Instillation of intravesical gentamicin requires the following supplies: sterile gloves, gentamicin, 0.9% normal saline, sterile cup, 60 cc syringe, and bed pad (chuck). Instillation of intravesical LGG requires the following supplies: sterile gloves, 6 or 8 LGG capsules depending ^^^^^^^^^^^^%^^%^^^^^ ^^^D!^^^^^^^^^^^^^^^!^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^%^D-^^^^^^^^^^^^^^^!^ additional in case of error), 0.9% normal saline, sterile cup, 60cc syringe, and bed pad (chuck). As we have successfully done to date, subjects are provided with (either face-to-face exchange or sent by mail) kits with materials for intravesical gentamicin and LGG instillations. The timing of installations is informed by Goal 1 & 2 described above. Intervention [00343] Gentamicin intravesical instillation is 480 mg gentamicin diluted in 1 L normal saline. 60cc (28.8 mg) of the solution is instilled into the bladder after drainage of urine is ^^^^^^^^^^^^^^^^^^^^^*^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^%^^^^^^^^^^^^^^^^^^^heterization. Participants are instructed to instill gentamicin twice daily for five days (10 total doses). The first instillation occurs after the first catheterization of the morning. [00344] For the intravesical LGG, participants are instructed to mix the contents of 1 LGG capsule into 45cc sterile 0.9% saline. After mixing, participants draw up the 45cc liquid LGG mixture into a 60cc syringe and instill via the intermittent catheter after the last catheterization prior to going to bed. Participants receive 4 or 6 LGG capsules (2 additional capsules/participant, depending on randomization group) and repeat this process every 12 hours until s/he has completed assigned dosing, according to randomization group. Participant study completion [00345] Subjects remain in the study for up to 9-10 weeks depending on the results of aims 1-2 with respect to whether gentamicin can be administered with, or prior to, LGG. Participation begins 28 days prior to initiation of the interventions and ends after the final (Day 28 post- intervention completion) urine sample and USQNB-IC. Participants are asked to return any unused gentamicin and LGG. The research pharmacy dispenses all gentamicin and LGG and count (and collect, if necessary) any unused instillate and capsules to maintain counts. See Table 2 (below) for a schedule of assessments & urine samples. Measures and measurements USQNB-IC [00346] Randomized participants are instructed to complete the USQNB-IC weekly for 3 weeks to generate an estimate of “usual” symptom burden. Upon completion of the 3^rd weekly USQNB-IC (day 14), participants are instructed to initiate the intervention if no USQNB-IC A or B1 symptoms are reported, and no UTI is present. If A and B1 symptoms are present on the 3^rd weekly USQNB-IC, participants begin USQNB-IC monitoring daily up to 14d (for a total of 28d USQNB monitoring) and may initiate the intervention once the USQNB-IC A and B1 symptoms are absent for 24h. If s/he continues to report USQNB-IC A and B1 symptoms from day 14 through day 28, s/he will be excluded. After at the baseline USQNB-IC data collection and no USQNB-IC A or B1 symptoms, participants are instructed to start the intervention. During the 5–7-day period of the intervention, participants will complete the USQNB-IC daily. After the intervention is complete, participants complete the USQNB-IC at the time of urine sampling (24h, 7d, 14d and 28d post last instillation). International SCI Lower Urinary Tract Function Basic Data Set [00347] A tool to describe urinary tract impairment, awareness of need to empty the bladder, main bladder emptying method, medications used for bladder management, surgeries, and change in urinary symptoms in the past year. Completed at each assessment. International SCI Core Data Set [00348] Includes date of injury, dates of initial hospitalization admission and discharge, neurological data. Completed at initial assessment only. NINDS Medical History CDE [00349] A brief medical history completed at initial assessment. NINDS Prior and Concomitant Medications CDE [00350] Contains name of medication, reason for medication, medication dose, frequency, start and end dates, and freetext. Completed at each assessment. Urine Collection and Shipment [00351] Subjects are provided materials for 8 urine collections and shipment of these to our laboratory (materials for 6 urine samples and 2 extra in case of error). Subjects are instructed in urine collection, storage, and shipping. Participants collect six 50-100ml urine samples for 16S sequencing (samples 1 and 2) and qPCR (samples 1-6). Urine is collected from a new, unused intermittent catheter under sterile conditions. Subjects are instructed to add AssayAssure (a DNA-stabilizing preservative agent) to each sample, mix, freeze, and then ship. DNA Isolation [00352] Once samples are received in Chicago, 1mL of each urine is transferred to 96 well deep well plates and centrifuged at 1600 x g for 10 minutes. Supernatant is aspirated leaving 100 uL of urine along with pelleted material at the bottom, unperturbed. Microbial DNA is extracted using cell wall digestive enzymes (lysozyme, lysostaphin, mutanolysin, and achromopeptidase) along with Qiagen's DNeasy Blood and Tissue kit. To assess potential DNA contamination, an extraction negative control (no urine) is processed and analyzed with the samples. To ensure reproducibility, each sample is extracted and analyzed in triplicate. 16S rRNA sequencing (urine samples #1 and #2) [00353] Extracted DNA will be processed using Zymo Research’s Quick-16S kit with phased primers targeting the V4 regions of the 16S gene (5’-GTGYCAGCMGCCGCGGTAA- 3’, 5’-GGACTACNVGGGTWTCTAAT-3’) (SEQ ID NO: 1). Following clean up and normalization, samples are sequenced on a P1600cyc NextSeq2000 Flowcell to generate 2x301bp PE reads. Adapters are trimmed. 16s sequencing is used on sample1 to determine baseline urobiome and to develop qPCR primers for comparison with post-intervention urine ^^^^^^^^^^^^^^^^^^^^^^^2 to determine to what extent intravesical gentamicin altered the urobiome. <^^^^^^^^^^^^9^^^^^^^^^^=^^^^^3^^^^^^^^ <9=3^^^^^^^^samples #1-6) [00354] Primers directed to LGG and from taxa identified by 16S analysis, and prioritized by the researchers (i.e., suspected uropathogens), are used. 10 µL reaction volume containing 2 µL of sample DNA, 0.3 µL forward and reverse primers, and 5 µL of 2x SsoFast EvaGreen supermix. Cycling temperatures are determined based on specific primers and calculated melting temperature but will generally be, 98˚C for 2 mins, followed by 40 cycles of 98ºC for 30 sec, 55-60ºC for 10 sec, 60ºC for 45 sec. Standardized concentration of comparable laboratory strains’ DNA are used to aid determination of sample DNA concentration. The range of detection is 2 pg/µL – 20 ng/µL. Study Variables Independent Variable [00355] Intravesical gentamicin-LGG dose (group: LGG high or LGG low). Sex is a stratifying, not an independent, variable. No inferences or comparisons are made based on sex. Dependent Variables [00356] We define “successful bladder colonization” by LGG to be an increase of ≥30% in its abundance (amplicon sequence variants [ASV] by qPCR) compared to the baseline value obtained immediately prior to the first dose of gentamicin. This increase is relative to the baseline value unless the baseline sample had zero LGG, in which case the increase is absolute. We determine, from urine samples, if each individual did/did not meet this definition of success and summarize rates of success at 24h, and 7, 14 and 28 days after final LGG instillation. A secondary indicator of success is based on the uropathogen to Lactobacillaceae (U/L ratio), where L is any member of the family Lactobacillaceae, including LGG. For this exploratory indicator, “successful bladder colonization” is defined as in increase in the U/L ratio of at least 25% from baseline, and will assess for success under this definition 24 h, and 7, 14 and 28 days after final LGG instillation. We also determine if and how often these 2 definitions of "success" co-occur. The number of men and women who meet the definitions of "successful colonization" with LGG are computed based on comparisons of samples 2-6 to sample 1 (baseline). Anyone who does not meet the given definition of "success" is counted as a “colonization failure” at the time of that urine sample. [00357] 16S analyses are conducted on samples #1 and #2 (pre- and post-gentamicin) only to determine which uropathogens are present in each individual at baseline and to determine if the gentamicin treatment was effective at eliminating them. qPCR analyses are performed on all urine samples using pan-Lactobacillaceae, LGG and prioritized uropathogen primers pairs. 8^^^^^^^^^^^^^^^^^^^^^^^<9=3^^^^^^^^^E^^^^^^^^^^AB6^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ assayed taxon. Also, we collect USQNB symptom burden prior to intervention, the 0-12 days of intervention, and 28 days post intervention, and estimate symptom burden for each. Exploratory analyses of these 2 burden estimates determine if changes in 16S and qPCR results correspond to any aspect of symptom burden. Symptom burden during the period of gent+LGG is used to supplement safety data. Analysis [00358] Baseline demographics and clinical characteristics are reported according to CONSORT guidelines. The size of any chance group imbalances is described, but no formal significance testing of sex differences is performed. Analysis is performed using an intent to treat approach, with subjects analyzed in the group assigned. Sample sizes have accounted for 20% potential attrition, so no imputation is performed in the instance of missing data. Data management and statistical analysis are performed using the latest versions of SPSS (29 or above) and R (4.3.1 or above). Outcomes [00359] As indicated above, we study two definitions of “successful bladder colonization” by LGG (1. an increase of ≥30% in its abundance (by qPCR) compared to the baseline value ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^%^^^^^^^^^^^^^^^!^^^^^^^^^^^^^^^^^^^^^")7^^^^^^^^^^ at least 25% from baseline. We serially assess success under each definition per Table 2. Statistical analysis [00360] Analysis uses an intent-to-treat approach, with men and women analyzed in assigned treatment groups. Success rates are estimated under the two definitions at four timepoints relative to baseline (see Table 2) for samples 3, 4, 5, and 6. Descriptive statistics only are planned for urine sample #1. Urine sample #2 answers three questions about the effectiveness of gentamicin (3 ^² analyses, separately by sex) because no LGG has been administered yet. Main analyses (^² on the success rates) is carried out separately for each definition of success and separately by sex as shown in Table 2. This yields a total of 2 (definitions of success) x 2 (sex) x 4 (success rate estimates from samples #3-#6) ^² ^^^^^^^^^^^^^^^^^^^^!^!^^^^^^^^^^^^^^^^ success vs. failure across the 2 dose arms (high/low). Sample sizes are planned with an extra 20% to accommodate loss during the intervention period and 28 day follow up, so no imputation ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^%^^^^^^^^>^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ for interaction effects (LGG dose x sex). Data management and statistical analysis is performed using the latest versions of SPSS (29 or above) and R (4.3.1 or above). We also qualitatively determine if differences exist in successful re-colonization rates based on sex, which is critically informative for the design of a future clinical trial.

_s ^y _ad 82 _.6 # 41 _.5 # _s ^y _ad 7 _.4 #o p ^o _c ^o _t #^a _l ^b _a ^h _c U^h _c ^e _r _t u ⁿ _e ^s _a o ^l- ^t _: ^l _i ^m 1 ^e _c ^d _i ^a _f ^, _s ^t _s ^d _e o ^{r # o} _t ^{n d} ^{? /} n o P _a _. G p ^e _{l a e} ^? _{e s i} p ^c _a ^t mm ^l dn g g ^s _{e i} u ⁿ _a ^{L n} _a ^c _c ⁿ _i3G # L ^o _c ^a _s ^d _i d^b _a ^h _{c /} U^h _c ^u _s ^f _e d_t ⁿ _{e e} ^t _{a ?} ² g ^e _lp ⁿ _i ^{d L} _/ ^x1 ⁿ _eg _i nⁱ _r ^m _a ^m _i ^{d o} _t ^{U )} _t n_e=^s _t mou G ^{s l} ^d _/ o_et ^? _s n^c ^t G ^t _{e a} d l n g a^{( s} _e ^t2 ^W _so ^{L d} ^o _e ⁿ _eg^t r ^{r g}o_c ^e _c o h ^e _f ⁿ _a ^N _/ n s^o _i ^ t p _r ^{^} _^ P _{t a} ^d _id^t _a ^f _at d _e ^{^} n o _^ _. o _: p ^Yp >2 ⁱ _r m ^o _r ⁿ _eu ^{x o} _r2 # P ^o _c 1 # u g^b _a 3 p ^ e_t od ^r _{a ,} Sⁿ _e ^t _c n a _s 6^G- ^a _l ^e _e ^{e n} c_eg _e1 +_r ⁿ o v h ^? _t ⁱ _t ^s _cP ⁿ _{i a} _. ^l _edn _? ^{t t} _a n ^p _i ⁱ _t p ^{e r} _c ^s _i R1 ^s u ^L _{/ a}h # _a b ^b _a U w^o _s _r u ^e _r ^s p _e ^t d_a C t _s P qE_I P o ^{N i} _t s RM E _eu UA S L Q_s n Power considerations [00361] The inferential (main) statistics involve a total of 2 (definitions of success) x 2 (sex) x 4 (success rate estimates) =16 individual 2 x 2 ^² analyses. Given the dynamic nature of the urobiome ecosystem, we treat the success rate, determined based on qPCR at each timepoint, to be independent, so uncorrected alpha of 0.05 is allocated to each analysis. We do not treat any individual result as "the answer" but rather as "a signal". The patterns of "wins" are explored by sample (3-6) and definition of "successful colonization". With N=10 completers in each dosing arm, and with a 1:1 allocation to dose arm for men and for women, our sample size has 80% power with α =0.05 to detect a difference in proportions of roughly 60%, which would be observed with, for example, 25% success in the “Low”, and 85% success in the “High” dose group within men. Descriptive statistics are used to summarize the independent measures listed above and to estimate pre-intervention and post-intervention symptom burden during the 28 days before/after the intervention. Null hypothesis significance testing is not used on any of the secondary analyses and do not plan inference tests for anything other than estimating whether dose (high/low) affects likelihood of successful colonization by lactobacillus at the end of the combined treatment (i.e., for sample 3 vs 1). The total sample (20 men, 20 women) needed for this level of power and effect size ^^^^^^^^^!^E^^^^^^^^^^^^%^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ of intravesical instillation of LGG, we conservatively estimate the total “attrition” to be 20% and we have had no differences in drop out or loss to follow up depending on sex. Given this, N=24 are enrolled in each dosing arm (12 men and 12 women per dose level). [00362] Unpowered exploratory descriptive statistics are also be computed for the alpha and beta (where estimable) diversity index values, and ASV for each species individually, focusing on the top 10 with greatest abundance for each participant based on their results in each of the 6 urine samples. Patterns are explored that may emerge based on person, sex, or dose arm of which species tend to be reduced or most affected. Further, within sex group, it is anticipated that the gentamicin treatments will create a 'level playing field' favoring LGG in the urobiome as it reconstitutes. The before and after gentamicin levels of diversity (beta diversity) are compared in samples 1 and 2 within person using permutational multivariate analysis of variance (adonis) as implemented in the vegan R package. Significance is determined as an event that occurs in less than 5% of 10,000 permutations. Bonferroni or Benjamini-Hochberg FDR multiple test correction methods will be applied. All analyses will be performed separately by treatment arm in mothur, QIIME and RStudio (RStudioTeam 2015). Anticipated outcomes and alternative approaches [00363] A potential outcome is that effects are distinctly different for men and women. Most people with SCI/D are males who generally do not carry Lactobacillaceae, or females, also lacking in Lactobacillaceae. We have generated evidence that some males have Lactobacillaceae in their bladder ^^^^7;;^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ unclear whether this combination will lead to re-colonization in males. If not, this trial is informative about an alternative LBP appropriate for males. Successful completion of this aim informs design of a future clinical trial for efficacy. EXAMPLE 2 Consensus Guidelines for Likelihood of UTI Introduction [00364] Complicated UTI (cUTI) is highly prevalent among people with Spinal cord injury and disease (SCI/D), but neither consistent nor evidence-based guidelines exist. Here, we describe a 2-phase, mixed-methods study to develop consensus around diagnostic and decision-making criteria for cUTI among people with SCI/D and the clinicians who treat them. To establish consensus opinion around cUTI diagnosis we implemented a mixed methods protocol, incorporating psychometric design features. This mixed methods protocol integrates formal psychometric methods with large-scale evidence gathering to derive consensus around diagnostic guidelines for cUTI among people with NLUTD due to SCI/D, plus information on uptake (clinicians) and impact (patients). Design [00365] We refined the valid and reliable Urinary Symptom Questionnaires for Neurogenic Bladder (USQNB)-based decision-making algorithms with iterative input from multidisciplinary clinicians (targeting SCI PM&R, Urology, Infectious Disease, Primary Care, and Emergency Medicine) nationwide. We solicited 32 interviews with clinicians from these disciplines to inform the design of a survey. [00366] We deployed the survey through the SCIMS network and also shared invitations to complete the surveys internationally. This proceeded as a dynamic Delphi: respondents of the invitations to complete the survey commented on the complexity of the survey and we updated the directions (but not the questions) over time. Methods [00367] We have adapted three psychometric design features to structure the qualitative ^^^^^F^^^%^^^^^^^^^^+^^^^^^^^^^ =#6^^^&^^^%^^^^^^^^^^^^^^^^'^^^^^^^^^^^^^^^^^^^%^>^^^^^^^^ 6^%^^^^^^^(^^^^^^^G^^+^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ standard setting (range finding/pinpointing) for concretely describing the resulting decision- making features for each bladder management method. Focus Groups [00368] The elicitation of knowledge (CTA step 3) is the core purpose of our focus groups, emphasizing engagement with decision making and specifically if, and how, urinary symptoms, inflammatory biomarkers, and bacterial load are utilized across specialty and location. To facilitate the focus group work we will utilize the technical features of standard setting, which is used in psychometric projects to describe performance at the “conceptual boundary between acceptable and unacceptable levels of achievement”. Here we will encourage clinicians to consider the “conceptual boundary” between treatment decisions (e.g., “yes antibiotics”, “not antibiotics”) or other decisions (patient self-^^^^%^^^^^^^^^^^^^^^^^ ^^^^^^^^^%^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^&^^^^^^^^^^^^^^ unacceptable levels of achievement”. That is, whereas typical psychometric methods often include literal cut score determination (i.e., scores above the cut are “pass” and below it are “fail”), we ask clinicians to describe or represent the conceptual boundaries between treatment decisions. Using formal standard setting brings validity and reproducibility to the more subjective aspects of clinical decision making. Table 3 presents the published symptom profiles based on the USQNB-IC that were featured in the interviews and our survey (starting point). [00369] Focus groups and interviews followed a (single) standardized script. We will also conduct interviews, as needed, to ensure that we have equal representation from the medical specialties listed above. These will be audio recorded and imported into Dedoose, a cloud-based qualitative data analysis software where data are parsed and coded. Coders on staff who are familiar with the software and thematic analysis will use a collaborative, iterative method of analysis to identify themes. We will continue to explore clinician perspectives on the decisions until the data are saturated, e.g. no new themes emerge. Themes will be member checked for accuracy and validity with focus group participants who will are asked to review written summaries cumulatively at the completion of the thematic data analysis. We will be able to leverage the expertise and experience of our research team to ensure that the outputs of the thematic analyses represent Action Needed clinical decisions. Coders have completed their training and have experience with the interviewing and software, and the iterative thematic analysis includes multiple coders conducting the analyses and checking each other’s work. When themes conflict, the research group discusses options. Either the investigators reach consensus, or new questions are integrated into the interview scripts. [00370] We ask panelists about their use of biomarkers, pyuria, and any bacterial load evidence used in clinical decision-making. Delphi Survey [00371] We refined the decision-making profiles resulting from focus groups into a survey to be deployed nationwide using the dynamic Delphi method to achieve consensus. Iqbal & Pipon-Young (2009) note that the first Delphi round may be used to establish the aspects those being surveyed will consider. We will have five clinical profiles and over 25 individual symptoms (by bladder management method) for participants to consider, we plan one or at most two rounds for this national survey. As Iqbal & Pipon-Young articulate, high response rates are essential to consensus building, and additional rounds may create fatigue in respondents. For Delphi respondents who do not agree with any aspect of the beta guidelines, we will seek permission to follow up for additional input. [00372] We determined that we would treat 80% agreement with the decision and the recommendation (UTI likelihood assessment and recommended clinical advice). Considering the three USQNB instruments and the six profiles based on symptoms and types of symptoms, there were a total of 18 decisions participants were asked about. Additional questions were also included. Results [00373] For the 18 questions about the likelihood of a symptomatic UTI and clinical decision. [00374] Voiders: Agreement <80% for profile 4. [00375] Intermittent Catheters: Agreement <80% for profiles 2 & 4. [00376] Indwelling Catheters: Agreement <80% for profiles 2 & 4. Profile 6 Profile 1. Higher likelihood of symptomatic UTI; Decision: work up based on clinical evaluation, including UA/UC NO CHANGES TO PROFILE 1 (consensus achieved) - ADD "symptomatic Profile 2. Moderate likelihood of symptomatic UTI; Decision: work based on clinical evaluation, UA/UC Symptom type: Other Profile: 2 Proposed change: from "medium likelihood of UTI" to "moderate likelihood of UTI"; - ADD "symptomatic" Profile 3. Lower likelihood of symptomatic UTI; Decision: Self-manage urinary symptoms NO CHANGES TO PROFILE 3 (consensus achieved) - ADD "symptomatic" Profile 4. Low to Moderate likelihood of symptomatic UTI; Decision: Consider evaluation with UA & other genitourinary assessment as indicated, Proposed change: from "lower likelihood of UTI" to "low to moderate likelihood of symptomatic UTI"; - ADD "symptomatic" Proposed change: Decision from "consider evaluation of bladder function" to "Consider evaluation with UA & other genitourinary assessment as indicated, including bladder pathophysiology" Profile 5. Lower likelihood of symptomatic UTI; Decision: Advise patient to self-manage and monitor NO CHANGES TO PROFILE 5 (consensus achieved) - ADD "symptomatic" Profile 6. UTI lowest likelihood of symptomatic UTI; Decision: Advise patient to self-monitor NO CHANGES TO PROFILE 6 (consensus achieved) - ADD "symptomatic" Based on these changes, the final decision-making algorithm is summarized in Table 4, below. Table 4. Profiles and clinician's decisions reflecting combinations of A, B1, and B2 type USQNB symptoms that suggest the highest likelihood of UTI (based on Tractenberg et al. 2023). NB: profile 1 is profile 1; profile 2 became profile 3 and profile 3 became profile 2;

Claims

Having described the invention, the following is claimed: 1. A method of treating and/or preventing urobiome dysbiosis in a subject in need thereof, the method comprising intravesicularly administering to the subject a therapeutically effective amount of two or more of an antimicrobial agent, an antispasmodic agent, and a live biotherapeutic product (LBP).

2. The method of claim 1, wherein the antimicrobial agent and the LBP are administered sequentially to the subject.

3. The method of claim 1, wherein the antimicrobial agent is administered for a period of time before the administration of the LBP.

4. The method of claim 3, wherein the antimicrobial agent is administered to the subject about 1 hour, about 2 hours, about 4 hours, about 8 hours, about 12 hours, about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about 1 week, about 2 weeks or more before administration of the LBP.

5. The method of claim 1, wherein the LBP is administered to the subject about 1 hour, about 2 hours, about 4 hours, about 8 hours, about 12 hours, about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about 1 week, about 2 weeks or more after administration of the antimicrobial agent.

6. The method of claim 1, wherein the LBP is administered concurrently with the antibiotic for a period of time before the final administration of the antimicrobial agent.

7. The method of claim 6, wherein the LBP is administered concurrently with the antimicrobial agent for about 6 hours, about 12 hours, about 1 day, about 2 days, about 3 days, about 4 days or more.

8. The method of claim 1, wherein the LBP is a probiotic treatment.

9. The method of claim 8, wherein the probiotic treatment includes a Lacticaseibacillus or Lactobacillus probiotic bacterial species.

10. The method of claim 9, wherein the Lacticaseibacillus probiotic bacterial species is Lacticaseibacillus rhamnosus GG (LGG).

11. The method of claim 9, wherein the Lactobacillus probiotic bacterial species is Lactobacillus crispatus.

12. The method of claim 1, wherein the antimicrobial agent is selected from the group consisting of an antibiotic, antiseptic, antiviral, antifungal and antiparasitic agent.

13. The method of claim 12, wherein the antimicrobial is an antibiotic.

14. The method of claim 13, the antibiotic selected from the group consisting of gentamicin, ampicillin, tobramycin, neomycin, polymyxin, amoxicillin/clavulanate, ceftriaxone, cephalexin, cefpodoxime, cefdinir, cefadroxil, ciprofloxacin, fosfomycin, levofloxacin, nitrofurantoin, trimethoprim/sulfamethoxazole, and combinations thereof.

15. The method of claim 14, wherein the antibiotic is gentamicin.

16. The method of claim 1, the antispasmodic agent selected from the group consisting of oxybutynin (Ditropan), tolterodine (Detrol), mirabegron (Myrbetriq), trospium, flavoxate, fesoterodine, darifenacin, solifenacin, hyoscyamine, and vibegron.

17. The method of claim 16, wherein the antispasmodic agent is oxybutynin (Ditropan).

18. The method of claim 1, wherein the antimicrobial agent, and/or the antispasmodic agent, and/or the LBP are bladder instillation treatments that are intravesicularly administered to the subject.

19. The method of claim 1, wherein the antimicrobial agent, and/or the antispasmodic agent, and/or the LBP is self-administered by the subject.

20. The method of claim 19, further comprising providing to the subject preparation instructions for preparing and self-administering the antimicrobial agent, and/or the antispasmodic agent, and/or the LBP.

21. The method of claim 1, wherein the subject has a spinal cord injury or disorder (SCI/D) and/or neurogenic lower urinary tract dysfunction (NLUTD).

22. The method of claim 1, wherein the subject manages their bladder using intermittent catheterization (IC).

23. The method of claim 1, wherein the subject manages their bladders using indwelling catheterization (IDC).

24. The method of claim 1, wherein the urobiome dysbiosis is a urinary tract infection (UTI).

25. The method of claim 1, wherein the subject does not have urobiome dysbiosis when treatment begins.

26. The method of claim 1, wherein urobiome dysbiosis in the subject is characterized by the overabundance of extended-spectrum beta-lactamase (ESBL) producing uropathogens in the lower urinary tract of the subject.

27. The method of claim 1, wherein the urobiome dysbiosis is characterized by the subject having one or more lower urinary tract symptoms (LUTS).

28. The method of claim 1, wherein the antimicrobial agent, and/or the antispasmodic agent, and/or the LBP is formulated in a pharmaceutically acceptable carrier.

29. The method of claim 28, wherein the pharmaceutically acceptable carrier includes citric acid and/or acetic acid.

30. The method of claim 1, wherein the therapeutically effective amount of two or more of the antimicrobial agent, the antispasmodic agent, and the LBP is the amount required to reduce the abundance of native and/or uropathogenic bacterial species in the urinary tract and allow for colonization or recolonization of the LBP in the urinary tract of the subject.

31. The method of claim 30, wherein the LBP is a probiotic bacterial species, and wherein colonization or recolonization of the probiotic bacterial species in the urinary tract of the subject is defined as the urobiome of the urinary tract having a probiotic bacterial density of about 10³ to about 10⁴ CFU/mL.

32. The method of claim 1, wherein the therapeutically effective amount of two or more of the antimicrobial agent, the antispasmodic agent, and the LBP is the amount required to prevent, inhibit, or reduce a UTI and/or one or more LUTS in the subject.

33. A system for selecting a treatment for urobiome dysbiosis in a subject, comprising: screening the subject for urobiome dysbiosis or the risk of developing ^^^^^^^^^^^^^^^^^^^^^^^ selecting a proper treatment if the subject has urobiome dysbiosis or the subject’s risk of developing urobiome dysbiosis exceeds a threshold, wherein the proper treatment includes the intravesical administration of a therapeutically effective amount of two or more of an antimicrobial agent, an antispasmodic agent, and a live biotherapeutic product (LBP) to the subject.

34. The system of claim 33, wherein the step of screening the subject for urobiome dysbiosis or the risk of developing urobiome dysbiosis comprises performing a urine test on a urine sample obtained from the subject, wherein the test determines the abundance of one or more uropathogenic bacterial species and/or the abundance of one or more probiotic bacterial species in the sample.

35. The system of claim 33, wherein the step of screening the subject for urobiome dysbiosis or the risk of developing urobiome dysbiosis comprises providing a questionnaire to the subject, wherein the subject completes the questionnaire, and determining the presence of urobiome dysbiosis or the risk of developing urobiome dysbiosis in the subject based on the data from the questionnaire.

36. The system of claim 35, wherein the questionnaire comprises questions related to the frequency of urinary symptoms, degree of severity of urinary symptoms, and/or impact of urinary symptoms in the subject.

37. The system of claim 33, wherein the antimicrobial agent and the LBP are administered sequentially to the subject.

38. The system of claim 33, wherein the antimicrobial agent is administered before the administration of the LBP for a period of time.

39. The system of claim 38, wherein the antimicrobial agent is administered to the subject about 1 hour, about 2 hours, about 4 hours, about 8 hours, about 12 hours, about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about 1 week, about 2 weeks or more before administration of the LBP.

40. The system of claim 33, wherein the LBP is administered to the subject about 1 hour, about 2 hours, about 4 hours, about 8 hours, about 12 hours, about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about 1 week, about 2 weeks or more after administration of the antimicrobial agent.

41. The system of claim 33, wherein the LBP is administered concurrently with the antimicrobial agent for a period of time before the final administration of the antibiotic.

42. The system of claim 41, wherein the LBP is administered concurrently with the antimicrobial agent for about 6 hours, about 12 hours, about 1 day, about 2 days, about 3 days, about 4 days or more.

43. The system of claim 33, wherein the LBP is a probiotic treatment.

44. The system of claim 43, wherein the probiotic treatment includes a Lacticaseibacillus or Lactobacillus probiotic bacterial species.

45. The system of claim 44, wherein the Lacticaseibacillus probiotic bacterial species is Lacticaseibacillus rhamnosus GG (LGG).

46. The system of claim 44, wherein the Lactobacillus probiotic bacterial species is Lactobacillus crispatus.

47. The system of claim 33, wherein the antimicrobial agent is selected from the group consisting of an antibiotic, antiseptic, antiviral, antifungal and antiparasitic agent.

48. The system of claim 47, wherein the antimicrobial agent is an antibiotic.

49. The system of claim 48, the antibiotic selected from the group consisting of gentamicin, ampicillin, tobramycin, neomycin, polymyxin, amoxicillin/clavulanate, ceftriaxone, cephalexin, cefpodoxime, cefdinir, cefadroxil, ciprofloxacin, fosfomycin, levofloxacin, nitrofurantoin, trimethoprim/sulfamethoxazole, and combinations thereof.

50. The system of claim 49, wherein the antibiotic is gentamicin.

51. The system of claim 33, the antispasmodic agent selected from the group consisting of oxybutynin (Ditropan), tolterodine (Detrol), mirabegron (Myrbetriq), trospium, flavoxate, fesoterodine, darifenacin, solifenacin, hyoscyamine, and vibegron.

52. The system of claim 51, wherein the antispasmodic agent is oxybutynin (Ditropan).

53. The system of claim 33, wherein the antimicrobial agent, and/or the antispasmodic agent, and/or the LBP are bladder instillation treatments that are intravesicularly administered to the subject.

54. The system of claim 33, wherein the antimicrobial agent, and/or the antispasmodic agent, and/or the LBP is/are self-administered to the subject.

55. The system of claim 54, further comprising providing to the subject preparation instructions for preparing and administering the antimicrobial agent, and/or the antispasmodic agent, and/or the LBP.

56. The system of claim 33, wherein the subject has a spinal cord injury or disorder (SCI/D) and/or neurogenic lower urinary tract dysfunction (NLUTD).

57. The system of claim 33, wherein the subject manages their bladder using intermittent catheterization (IC).

58. The system of claim 33, wherein the subject manages their bladders using indwelling catheterization (IDC).

59. The system of claim 33, wherein the urobiome dysbiosis is a urinary tract infection (UTI).

60. The system of claim 33, wherein the subject does not have urobiome dysbiosis when treatment begins.

61. The system of claim 33, wherein the antimicrobial agent, and/or the antispasmodic agent, and/or the LBP formulated in a pharmaceutically acceptable carrier.

62. The system of claim 61, wherein the pharmaceutically acceptable carrier includes citric acid and/or acetic acid.

63. The system of claim 33, wherein the therapeutic amount of the antimicrobial agent, and/or antispasmodic agent, and the LBP is the amount required to reduce the abundance of native and/or uropathogenic bacterial species in the urinary tract and allow colonization or recolonization of the LBP in the urinary tract of the subject.

64. The system of claim 63, wherein the LBP is a probiotic bacterial species, and wherein colonization or recolonization of the probiotic bacterial species in the urinary tract of the subject is defined as the urobiome of the urinary tract having a probiotic bacterial density of about 10³ to about 10⁴ CFU/mL.

65. The method of claim 33, wherein the therapeutic amount of the antimicrobial agent and the LBP is the amount required to prevent, inhibit, or reduce the frequency, degree of severity and/or impact of a UTI and/or one or more LUTS in the subject.

66. A kit for preventing and/or treating urobiome dysbiosis in a subject in need thereof, the kit comprising: one or more doses of a therapeutically effective amount of two or more of an antimicrobial agent, an antispasmodic agent, ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ 7(9^^^^^^^ equipment necessary to perform self-administered therapy for the antimicrobial agent, and/or the antispasmodic agent, and/or the LBP.

67. The kit of claim 66, further comprising a plurality of urine diagnostic test, wherein the plurality of urine diagnostic tests comprises equipment necessary to perform a self-administered urine diagnostic test for the detection urobiome dysbiosis in urine, wherein the plurality of urine diagnostic tests comprises a plurality rapid screening urinary test strips and a plurality of urine collection containers.

68. The kit of claim 67, further comprising information relating to the urine diagnostic test and instructions on how to perform the urine diagnostic test.

69. The kit of claim 66, further comprising a plurality of UTI diagnostic test, wherein the plurality of UTI diagnostic tests comprises equipment necessary to perform a self-administered UTI diagnostic test for the detection of a UTI in urine, wherein the plurality of UTI diagnostic tests comprise a plurality of leukocyte esterase and nitrite rapid screening urinary test strips and a plurality of urine collection containers.

70. The kit of claim 69, further comprising information relating to the UTI diagnostic test and instructions on how to perform the UTI diagnostic test.

71. The kit of claim 66, further comprising information relating to the antibiotic, and/or the antispasmodic agent, and/or LBP and instructions on how to select and self- administer the antimicrobial agent, and/or the antispasmodic agent, and/or LBP.

72. The kit of claim 66, wherein the antimicrobial agent is gentamicin and the LBP is a Lacticaseibacillus rhamnosus GG (LGG) probiotic treatment.

73. The kit of claim 66, wherein the antimicrobial agent is gentamicin and the LBP is a Lactobacillus crispatus.

74. The kit of claim 66, wherein the antispasmodic agent is oxybutynin (Ditropan).

75. A method of determining the likelihood of a symptomatic urinary tract infection (UTI) in a subject, the method comprising: screening the subject for one or more urinary symptoms, the urinary symptoms selected from Action Needed, Bladder, Urine, and Other urinary symptoms, wherein the presence and/or absence of a combination of urinary symptoms correlates with a higher, moderate, low- moderate, lower, low, or lowest likelihood of symptomatic UTI.

76. The method of claim 75, the Action Needed symptoms selected from the group consisting of bladder spasm frequency/discomfort, fever, increase in lower body tone or spasticity, difficulty ambulating, difficulty thinking/mental fogginess/forgetfulness, mental slowing, dizziness, headache, flushing of chest/neck/face, bladder discomfort, sweating, autonomic dysreflexia, abdominal/suprapubic pain and multiple sclerosis (MS) flare up.

77. The method of claim 75, the Bladder symptoms selected from the group consisting of blood in urine, urinary urgency, incontinence/urine leakage, increase frequency of urination, sensation of urinary urgency, inability to fully empty bladder, weak urine stream, change in quality of pain when passing urine, change in quality of pain during catheterization, increase in catheterization frequency, blood clots in urine, and reduced urine volume/catheterization volume.

78. The method of claim 75, the Urine symptoms selected from the group consisting of malodorous urine, dark urine, and cloudy/sediment in urine.

79. The method of claim 75, the Other symptoms selected from the group consisting of increased fatigue/lethargy/weakness, chills, vomiting, loss of appetite, altered sleep patterns, muscle ache increase in positional pain, pain in the legs, change in bowel patterns, diarrhea, numbness/tingling in extremities, pain below level of injury, discharge/redness/sensitivity around catheter site, sense of burning in extremities/throughout the body, increase or decrease from normal blood pressure, malaise/feeling unwell, nausea, generalized abdominal discomfort or bloating, back pain, and irritability

80. The method of claim 75, the subject comprising a subject managing their bladder via urinary voiding (V), wherein: the Action Needed symptoms are selected from the group consisting of bladder spasm frequency/discomfort, fever, increase in lower body tone or spasticity, difficulty ambulating, difficulty thinking/mental fogginess/forgetfulness, sweating, autonomic dysreflexia and multiple sclerosis (MS) ^^^^^^^^^ the Bladder symptoms are selected from the group of blood in urine, urinary urgency, incontinence/urine leakage, increase frequency of urination, sensation of urinary urgency, inability to fully empty bladder, weak urine stream, and reduced urine volume/catheterization ^^^^^^^ the Urine symptoms are selected from malodorous urine, dark urine, and ^^^^^^)^^^^^^^^^^^^^^^^^^^^^^^ the Other symptoms are selected from the group consisting of increased fatigue/lethargy/weakness, chills, vomiting, malaise/feeling unwell, and nausea.

81. The method of claim 75, the subject comprising a subject managing their bladder via intermittent catheterization (IC), wherein: the Action Needed symptoms are selected from the group consisting of bladder spasm frequency/discomfort, fever, increase in lower body tone or spasticity, dizziness, headache, ^^^^^^^^^)^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ the Bladder symptoms are selected from the group consisting of blood in urine, urinary urgency, incontinence/urine leakage, change in quality of pain when passing urine, change in quality of pain during catheterization, increase in catheterization frequency, and decreased ^^^^^^^^^^^^^^^)^^^^^^^^^*^^^^^^^^^^^^^ the Urine symptoms are selected from the group consisting of malodorous urine, dark ^^^^^^^^^^^^^^^^^)^^^^^^^^^^^^^^^^^^^^^^^ the Other symptoms are selected from the group consisting of fatigue/lethargy/weakness, loss of appetite, altered sleep patterns, muscle ache increase in positional pain, pain in the legs, change in bowel patterns, malaise/feeling unwell, nausea, generalized abdominal discomfort or bloating, back pain, and irritability.

82. The method of claim 75, the subject comprising a subject managing their bladder via indwelling catheterization (IDC), wherein: the Action Needed symptoms are selected from the group consisting of bladder spasm frequency/discomfort, fever, increase in lower body tone or spasticity, flushing of chest/neck/face, bladder discomfort, sweating, autonomic dysreflexia, and abdominal/supra^^^^^^^^^^^ the Bladder symptoms are selected from the group consisting of blood in urine, urinary ^^%^^^^^^^^^^^^^^^^^^)^^^^^^^^^+^%^^^^^^^^^^^^^^^^^^^^^^^^^^^^ the Urine symptoms are selected from the group consisting of malodorous urine, dark urine, ^^^^^^^^^^)^^^^^^^^^^^^^^^^^^^^^^^ the Other symptoms are selected from the group consisting of fatigue/lethargy/weakness, diarrhea, numbness/tingling in extremities, pain below level of injury, discharge/redness/sensitivity around catheter site, sense of burning in extremities/throughout the body, increase or decrease from normal blood pressure, generalized abdominal discomfort or bloating, back pain, and irritability.

83. The method of claim 75, wherein the subject is determined to have a higher likelihood of symptomatic UTI, the subject having: at least one Action Needed symptom and one or more Bladder or Urine symptoms.

84. The method of claim 75, wherein the subject is determined to have a moderate likelihood of symptomatic UTI, the subject having: ^^^^^^^^^^^^^6^^^^^^B^^^^^^^^^^^^^^^^^^*^^^^(^^^^^^^^^^"^^^^^^^^^^^^^^^^^^ zero Action Needed symptoms, one or more Bladder symptoms, and one or more Urine symptoms.

85. The method of claim 75, wherein the subject is determined to have a low- moderate likelihood of symptomatic UTI, the subject having: zero Action Needed symptoms, 4 or more Bladder symptoms, and zero Urine symptoms.

86. The method of claim 75, wherein the subject is determined to have a lower likelihood of symptomatic UTI, the subject having: zero Action Needed symptoms, zero Bladder symptoms, one or more Urine symptoms, ^^^^^^^^^^^^^^^^,^^^^^^^^^^^^^^^^^ zero Action Needed symptoms, 1-3 Bladder symptoms, zero Urine symptoms and zero Other symptoms.

87. The method of claim 75, wherein the subject is determined to have a low likelihood of symptomatic UTI, the subject having: zero Action Needed symptoms, zero Bladder symptoms, zero Urine symptoms, and one or more Other symptoms.

88. The method of claim 75, wherein the subject is determined to have a lowest likelihood symptomatic UTI, the subject having: zero Action Needed symptoms, zero Bladder symptoms, zero Urine symptoms, and zero Other symptoms.

89. The method of claim 75, the subject having neurogenic lower urinary tract dysfunction (NLUTD, also known as a neurogenic bladder (NB)).

90. A method of selecting treatment for a urinary tract infection (UTI) in a subject, comprising: screening the subject for one or more urinary symptoms, wherein the urinary symptoms selected from Action Needed, Bladder, Urine, and Other urinary symptoms, and wherein the presence and/or absence of a combination of urinary symptoms correlates with a higher, moderate, low-^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^+^^^^^^^^^^^^^^^^^^^^^^^"#$^^^^^ selecting a UTI treatment based on the determined likelihood of symptomatic UTI in the subject.

91. The method of claim 90, wherein the subject is determined to have a higher likelihood of symptomatic UTI, and wherein the treatment includes administering a therapeutically effective amount of an antimicrobial agent and/or an antispasmodic agent.

92. The method of claim 91, wherein the antimicrobial agent includes an antibiotic agent.

93. The method of claim 90, wherein the subject is determined to have a moderate, low-moderate, or lower likelihood of symptomatic UTI, and wherein the treatment includes the administration of a therapeutically effective amount of a live biotherapeutic product (LBP) comprising Lacticaseibacillus rhamnosus and/or Lactobacillus crispatus.

94. The method of claim 93, wherein the LBP is a bladder instillation treatment administered intravesicularly to the subject.

95. The method of claim 93, wherein the LBP treatment is administered to the subject by a health care professional.

96. The method of claim 93, wherein the LBP treatment is self-administered by the subject.

97. The method of claim 96, further comprising providing to the subject preparation and/or administration instructions for the LBP treatment.

98. The method of claim 93, the therapeutically effective amount of an LBP comprising the amount required to reduce the frequency, degree of severity and/or impact of one or more urinary symptoms on the subject.

99. The method of claim 90, wherein the subject is determined to have a low or a lowest likelihood of symptomatic UTI, the treatment further comprises continued monitoring of urinary symptoms in the subject.

100. The method of claim 99, wherein the continued monitoring of urinary symptoms includes self-monitoring urinary symptoms by the subject, and the method further comprising providing to the subject instructions for self-monitoring urinary symptoms.

101. The method of claim 90, the Action Needed symptoms selected from the group consisting of bladder spasm frequency/discomfort, fever, increase in tone or spasticity, difficulty ambulating, difficulty thinking/mental fogginess/forgetfulness, dizziness, headache, flushing of chest/neck/face, bladder discomfort, sweating, autonomic dysreflexia, abdominal/suprapubic pain and multiple sclerosis (MS) flare up.

102. The method of claim 90, the Bladder symptoms selected from the group consisting of blood in urine, urinary urgency, incontinence/urine leakage, increase frequency of urination, sensation of urinary urgency, inability to fully empty bladder, weak urine stream, change in quality of pain when passing urine, change in quality of pain during catheterization, increase in catheterization frequency, blood clots in urine, and reduced urine volume/catheterization volume.

103. The method of claim 90, the Urine symptoms selected from the group consisting of malodorous urine, dark urine, and cloudy/sediment in urine.

104. The method of claim 90, the Other symptoms selected from the group consisting of increased fatigue/lethargy/weakness, chills, vomiting, loss of appetite, altered sleep patterns, muscle ache increase in positional pain, pain in the legs, change in bowel patterns, diarrhea, numbness/tingling in extremities, pain below level of injury, discharge/redness/sensitivity around catheter site, sense of burning in extremities/throughout the body, increase or decrease from normal blood pressure, malaise/feeling unwell, nausea, generalized abdominal discomfort or bloating, back pain, and irritability.

105. The method of claim 90, the subject comprising a subject managing their bladder via urinary voiding (V), wherein: the Action Needed symptoms are selected from the group consisting of bladder spasm frequency/discomfort, fever, increase in lower body tone or spasticity, difficulty ambulating, difficulty thinking/mental fogginess/forgetfulness, sweating, autonomic dysreflexia and multiple sclerosis (MS) ^^^^^^^^^ the Bladder symptoms are selected from the group of blood in urine, urinary urgency, incontinence/urine leakage, increase frequency of urination, sensation of urgency/empty bladder, inability to fully empty bladder, weak urine stream, and reduced urine vol^^^)^^^^^^^^^*^^^^^^^^^^^^^ the Urine symptoms are selected from malodorous urine, dark urine, and ^^^^^^)^^^^^^^^^^^^^^^^^^^^^^^ the Other symptoms are selected from the group consisting of increased fatigue/lethargy/weakness, chills, vomiting, malaise/feeling unwell, and nausea.

106. The method of claim 16, the subject comprising a subject managing their bladder via intermittent catheterization (IC), wherein: the Action Needed symptoms are selected from the group consisting of bladder spasm frequency/discomfort, fever, increase in lower body tone or spasticity, dizziness, headache, ^^^^^^^^^)^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ the Bladder symptoms are selected from the group consisting of blood in urine, urinary urgency, incontinence/urine leakage, change in quality of pain when passing urine, change in quality of pain during catheterization, increase in catheterization frequency, and decreased ^^^^^^^^^^^^^^^)^^^^^^^^^*^^^^^^^^^^^^^ the Urine symptoms are selected from the group consisting of malodorous urine, dark ^^^^^^^^^^^^^^^^^)^^^^^^^^^^^^^^^^^^^^^^^ the Other symptoms are selected from the group consisting of fatigue/lethargy/weakness, loss of appetite, altered sleep patterns, muscle ache increase in positional pain, pain in the legs, change in bowel patterns, malaise/feeling unwell, nausea, generalized abdominal discomfort or bloating, back pain, and irritability.

107. The method of claim 90, the subject comprising a subject managing their bladder via indwelling catheterization (IDC), wherein: the Action Needed symptoms are selected from the group consisting of bladder spasm frequency/discomfort, fever, increase in lower body tone or spasticity, flushing of chest/neck/face, bladder discomfort, sweating, autonomic dysreflexia, and abdominal/supra^^^^^^^^^^^ the Bladder symptoms are selected from the group consisting of blood in urine, urinary ^^%^^^^^^^^^^^^^^^^^^)^^^^^^^^^+^%^^^^^^^^^^^^^^^^^^^^^^^^^^^^ the Urine symptoms are selected from the group consisting of malodorous urine, dark ^^^^^^^^^^^^^^^^^)^^^^^^^^^^^^^^^^^^^^^^^ the Other symptoms are selected from the group consisting of fatigue/lethargy/weakness, diarrhea, numbness/tingling in extremities, pain below level of injury, discharge/redness/sensitivity around catheter site, sense of burning in extremities/throughout the body, increase or decrease from normal blood pressure, generalized abdominal discomfort or bloating, back pain, and irritability.

108. The method of claim 90, the subject having neurogenic lower urinary tract dysfunction (NLUTD).

109. The method of claim 90, wherein the subject is determined to have a higher likelihood of symptomatic UTI, the subject having at least one Action Needed symptom and one or more Bladder or Urine symptoms.

110. The method of claim 90, wherein the subject is determined to have a moderate likelihood of symptomatic UTI, the subject having: ^^^^^^^^^^^^^6^^^^^^B^^^^^^^^^^^^^^^^^^*^^^^(^^^^^^^^^^"^^^^^^^^^^^^^^^^^^ zero Action Needed symptoms, one or more Bladder symptoms, and one or more Urine symptoms.

111. The method of claim 90, wherein the subject is determined to have a low- moderate likelihood of symptomatic UTI, the subject having: zero Action Needed symptoms, 4 or more Bladder symptoms, and zero Urine symptoms.

112. The method of claim 90, wherein the subject is determined to have a lower likelihood of symptomatic UTI, the subject having: zero Action Needed symptoms, zero Bladder symptoms, one or more Urine symptoms, ^^^^^^^^^^^^^^^^,^^^^^^^^^^^^^^^^^ zero Action Needed symptoms, 1-3 Bladder symptoms, zero Urine symptoms and zero Other symptoms.

113. The method of claim 90, wherein the subject is determined to have a low likelihood of symptomatic UTI, the subject having zero Action Needed symptoms, zero Bladder symptoms, zero Urine symptoms, and one or more Other symptoms.

114. The method of claim 16, wherein the subject is determined to have a lowest likelihood symptomatic UTI, the subject having: zero Action Needed symptoms, zero Bladder symptoms, zero Urine symptoms, and zero Other symptoms.41.

115. A method of treating or preventing a urinary tract infection (UTI) in a subject, the method comprising administering to the subject a therapeutically effective amount of a live biotherapeutic product (LBP), wherein the LBP includes Lacticaseibacillus rhamnosus and Lactobacillus crispatus.

116. The method of claim 115, wherein the Lacticaseibacillus rhamnosus is Lacticaseibacillus rhamnosus GG (LGG).

117. The method of claim 115, wherein the Lactobacillus crispatus is Lactobacillus crispatus CTV-05, Lactobacillus crispatus SJ-3C or Lactobacillus crispatus 262-1.

118. The method of claim 115, wherein the LBP is an LBP bladder instillation treatment administered intravesicularly to the subject.

119. The method of claim 115, the therapeutically effective amount comprising the amount required to reduce the frequency, degree of severity and/or impact of urinary symptoms on the subject.

120. The method of claim 115, wherein the subject has neurogenic lower urinary tract dysfunction (NLUTD).

121. The method of claim 115, wherein the subject has a spinal cord injury or disorder (SCI/D), spina bifida, and/or multiple sclerosis.

122. The method of claim 115, wherein the UTI is a Catheter-Associated Urinary Tract Infection (CAUTI).

123. The method of claim 115, wherein the subject manages their bladder using urinary voiding (V).

124. The method of claim 115, wherein the subject manages their bladder using intermittent catheterization (IC).

125. The method of claim 115, wherein the subject manages their bladders using indwelling catheterization (IDC).

126. The method of claim 115, wherein the LBP is administered to the subject by a health care professional.

127. The method of claim 115, wherein the LBP is self-administered by the subject.

128. The method of claim 127, further comprising providing to the subject preparation instructions for the LBP treatment.

129. The method of claim 115, further comprising administering to the subject one or more additional therapeutic agents, the one or more therapeutic agents selected from the group consisting of an additional probiotic bacterial species, an antimicrobial agent and an antispasmodic agent.

130. The method of claim 129, wherein the additional probiotic bacterial species is a Lacticaseibacillus or Lactobacillus probiotic bacterial species.

131. The method of claim 129, wherein the antimicrobial agent is an antibiotic.

132. The method of claim 115, the subject determined to have a moderate, low- moderate, or lower likelihood of symptomatic UTI, wherein the likelihood of symptomatic UTI is determined in the subject according to a method of any of claims 1-14.

133. A pharmaceutical composition for the treatment or prevention of a urinary tract infection (UTI), the composition comprising: a live biotherapeutic product (LBP), wherein the LBP includes a combination of Lacticaseibacillus rhamnosus and Lactobacillus crispatus.

134. The pharmaceutical composition of claim 133, wherein the Lacticaseibacillus rhamnosus is Lacticaseibacillus rhamnosus GG (LGG).

135. The pharmaceutical composition of claim 133, wherein the Lactobacillus crispatus is Lactobacillus crispatus CTV-05, Lactobacillus crispatus SJ-3C or Lactobacillus crispatus 262-1.

136. The pharmaceutical composition of claim 133, wherein the composition is a dried formulation.

137. The pharmaceutical composition of claim 133, further comprising a pharmaceutically acceptable carrier.

138. The pharmaceutical composition of claim 137, wherein the pharmaceutically acceptable carrier is formulated for intravesical, topical, intravaginal, and/or intraurethral administration.

139. The pharmaceutical composition of claim 137, wherein the composition is in a single dose form appropriate for intravesical, topical, intravaginal, and/or intraurethral administration.