CN116606761B - Bifidobacterium animalis subspecies BLa19 capable of relieving rheumatoid arthritis and application thereof - Google Patents
Bifidobacterium animalis subspecies BLa19 capable of relieving rheumatoid arthritis and application thereof Download PDFInfo
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- CN116606761B CN116606761B CN202310398435.5A CN202310398435A CN116606761B CN 116606761 B CN116606761 B CN 116606761B CN 202310398435 A CN202310398435 A CN 202310398435A CN 116606761 B CN116606761 B CN 116606761B
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- bifidobacterium animalis
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Abstract
The invention relates to an animal bifidobacterium lactis BLa19 capable of relieving rheumatoid arthritis and application thereof, which is named as an animal bifidobacterium lactis BLa19 strain with the preservation number of CGMCC No.24028. The strain has good gastric acid resistance, and can smoothly pass through the gastrointestinal tract to reach the small intestine to exert the effect of probiotics; can effectively relieve the symptoms of the rheumatoid arthritis model mice; the number of main dominant bacterial groups in the intestinal tract of a rheumatoid arthritis model mouse can be increased, so that the purpose of relieving arthritis is achieved; can reduce the rheumatoid factor in the serum of a rheumatoid arthritis model mouse; can increase the content of short chain fatty acid in the feces of the rheumatoid arthritis model mice.
Description
Technical Field
The invention belongs to the technical field of microbial cultivation, relates to an animal bifidobacterium lactis subspecies BLa19 capable of relieving rheumatoid arthritis and application thereof, and in particular relates to an animal bifidobacterium lactis subspecies BLa19 capable of relieving rheumatoid arthritis and application thereof in preparing medicines for preventing, improving or treating rheumatoid arthritis.
Background
Rheumatoid arthritis (Rheumatoid arthritis, RA) is a common chronic immune system disease with unknown etiology, and morning stiffness, pain, swelling, deformity, dysfunction and the like are the main clinical manifestations thereof, and RA poses a great threat to human health. Therefore, has great significance in preventing and treating rheumatoid arthritis.
At present, the clinical drug treatment and the clinical operation treatment are main treatment modes of RA, and the drug treatment comprises nonsteroidal anti-inflammatory drugs (NSAIDs), antirheumatic drugs (DMARDs) and glucocorticoids, and can reduce synovitis and systemic inflammation and relieve discomfort and pain of patients; however, these drugs do not necessarily have sufficient effects and have serious side effects including renal hepatotoxicity, which limits their clinical application.
The disturbance of immune balance in joints is currently considered to be a major feature of RA, and each immune cell plays an important role in maintaining the balance of immune function of the host and pathogenesis of RA. The intestinal tract is the largest immune organ of the host and a large number of microorganisms reside in the intestinal tract of the host within the intestinal mucosa. Studies have shown that the microbiota in the gut is disturbed and the gut-derived immune cells are activated and secrete pro-inflammatory factors, which alter the local and subsequent systemic immune response, ultimately contributing to the pathogenesis of RA.
How to provide a product capable of relieving the rheumatoid arthritis, which does not increase the drug resistance of the rheumatoid arthritis, does not cause adverse reaction to patients in the treatment process, and improves the clinical treatment effect of the rheumatoid arthritis, thus becoming a problem to be solved urgently.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide the bifidobacterium animalis subspecies of milk Bla19 capable of relieving rheumatoid arthritis and application thereof, in particular to the bifidobacterium animalis subspecies of milk Bla19 capable of relieving rheumatoid arthritis and application thereof in preparing medicaments for preventing, improving or treating the rheumatoid arthritis.
In order to achieve the aim of the invention, the invention adopts the following technical scheme:
in a first aspect, the invention provides a bifidobacterium animalis subspecies of milk Bla19 capable of alleviating rheumatoid arthritis, wherein the bifidobacterium animalis subspecies of milk Bla19 capable of alleviating rheumatoid arthritis is named as bifidobacterium animalis subspecies Bifidobacterium animalis subsp.lactis BLa19 strain, the preservation number is CGMCC No.24028, and the preservation date is 2021, 12 months and 2 days.
The invention separates and stores a new bifidobacterium animalis subspecies capable of relieving rheumatoid arthritis from a healthy infant fecal sample, and names the bifidobacterium animalis subspecies Bifidobacterium animalis subsp.lactis BLa19 strain which has good gastric acid resistance and can smoothly pass through the gastrointestinal tract to reach the small intestine to play a probiotic effect; can effectively relieve the symptoms of the rheumatoid arthritis model mice; the number of main dominant bacterial groups in the intestinal tract of a rheumatoid arthritis model mouse can be increased, so that the purpose of relieving arthritis is achieved; can reduce the rheumatoid factor in the serum of a rheumatoid arthritis model mouse; can increase the content of short chain fatty acids (acetic acid, propionic acid, isobutyric acid, butyric acid and valeric acid) in the feces of a rheumatoid arthritis model mouse. The strain is a probiotic, has high safety, does not generate drug resistance, and does not cause adverse reaction of patients.
In a second aspect, the present invention provides the use of bifidobacterium animalis subspecies gla 19 as described in the first aspect for the manufacture of a medicament for the prevention, amelioration or treatment of rheumatoid arthritis.
The bifidobacterium animalis subspecies of the invention, the BLa19 strain, can be used in related products alone or in combination with other strains.
In a third aspect, the present invention provides the use of bifidobacterium animalis subspecies lactis BLa19 capable of alleviating rheumatoid arthritis as described in the first aspect for the preparation of a rheumatoid factor inhibitor, interleukin 7 accelerator or peptidoglycan recognition protein 1 inhibitor for non-diagnostic and/or therapeutic purposes.
According to the research result of the present invention, the bifidobacterium animalis subspecies of the Bla19 has the effect of remarkably inhibiting the rheumatoid factor, the peptidoglycan recognition protein 1 and promoting the interleukin 7, so the result shows that the bifidobacterium animalis subspecies of the Bla19 can be used as a non-diagnostic and/or therapeutic rheumatoid factor inhibitor, an interleukin 7 promoter or a peptidoglycan recognition protein 1 inhibitor for research fields, such as research on the biological metabolism mechanism and behavior of more rheumatoid factors, interleukin 7 or peptidoglycan recognition proteins 1.
In a fourth aspect, the present invention provides a probiotic with a method of preventing, ameliorating or treating rheumatoid arthritis, the probiotic with a method of preventing, ameliorating or treating rheumatoid arthritis comprising the bifidobacterium animalis subsp.lacti BLa19 strain of subspecies lactis Bifidobacterium animalis.
Preferably, in the probiotic agent, the viable count of the bifidobacterium animalis subsp.lacti BLa19 strain is not less than 1×10 8 CFU/mL or 1X 10 8 CFU/g, e.g. 1X 10 8 CFU/mL、2×10 8 CFU/mL、5×10 8 CFU/mL、8×10 8 CFU/mL、1×10 9 CFU/mL、5×10 9 CFU/mL、1×10 10 CFU/mL, etc., and other specific point values within the numerical range may be selected, and will not be described in detail herein.
Preferably, the formulation of the probiotics can be freeze-dried powder, and the freeze-dried powder can be further prepared into formulations such as capsules, tablets and the like.
Preferably, the probiotic agent further comprises a protective agent and/or a co-additive.
The protective agent comprises skimmed milk powder.
The auxiliary additive comprises any one or a combination of at least two of fructo-oligosaccharide, galacto-oligosaccharide, xylo-oligosaccharide, isomalto-oligosaccharide, soybean oligosaccharide, inulin, spirulina, arthrospira, coriolus versicolor polysaccharide, stachyose, polydextrose, alpha-lactalbumin or lactoferrin.
In a fifth aspect, the present invention provides a complex probiotic having the ability to prevent, ameliorate or treat rheumatoid arthritis, said complex probiotic comprising bifidobacterium animalis subspecies Bifidobacterium animalis subsp.lactis BLa19 strain and lactobacillus casei Lactobacillus casei LC89 strain according to the first aspect; the preservation number of the lactobacillus casei Lactobacillus casei LC strain is CGMCC No.15409, and the preservation date is 2018, 3, 5.
The invention also creatively discovers that the bifidobacterium animalis subsp Bifidobacterium animalis subsp.lactis BLa19 strain can be used for preventing, improving or treating the rheumatoid arthritis by being compounded with the lactobacillus casei Lactobacillus casei LC strain, has an effect which is remarkably superior to that of a single microbial inoculum or other compound formulas, and shows that the BLa19 strain and the LC89 strain have a synergistic effect on relieving the rheumatoid arthritis symptoms.
Preferably, the mass ratio of the bifidobacterium animalis subspecies Bifidobacterium animalis subsp.lacti BLa19 strain to the lactobacillus casei Lactobacillus casei LC strain 89 is (2-4): 1, such as 2:1, 2.5:1, 3:1, 3.5:1, 4:1, etc., and other specific values within the numerical range may be selected, and will not be described in detail herein.
In the composite probiotic, the two strains have better synergistic effect when meeting the specific mass proportion relation.
Preferably, the composite probiotic agent further comprises a protective agent and/or a co-additive.
The protective agent comprises skimmed milk powder.
The auxiliary additive comprises any one or a combination of at least two of fructo-oligosaccharide, galacto-oligosaccharide, xylo-oligosaccharide, isomalto-oligosaccharide, soybean oligosaccharide, inulin, spirulina, arthrospira, coriolus versicolor polysaccharide, stachyose, polydextrose, alpha-lactalbumin or lactoferrin.
In a sixth aspect, the present invention provides a method of culturing bifidobacterium animalis subspecies gla 19 capable of alleviating rheumatoid arthritis according to the first aspect, the method comprising inoculating bifidobacterium animalis subspecies gla 19 on MRS medium for culturing.
Preferably, the temperature of the culture is 30-37 ℃, e.g., 30 ℃, 31 ℃, 32 ℃, 33 ℃, 34 ℃, 35 ℃, 36 ℃,37 ℃, etc.; the cultivation time is 18-24h, such as 18h, 19h, 20h, 21h, 22h, 23h, 24h, etc.; other specific point values within the numerical range can be selected, and will not be described in detail herein.
Compared with the prior art, the invention has the following beneficial effects:
the invention separates and stores a new bifidobacterium animalis subspecies capable of relieving rheumatoid arthritis from a healthy infant fecal sample, and names the bifidobacterium animalis subspecies Bifidobacterium animalis subsp.lactis BLa19 strain which has good gastric acid resistance and can smoothly pass through the gastrointestinal tract to reach the small intestine to play a probiotic effect; can effectively relieve the symptoms of the rheumatoid arthritis model mice; the number of main dominant bacterial groups in the intestinal tract of a rheumatoid arthritis model mouse can be increased, so that the purpose of relieving arthritis is achieved; can reduce the rheumatoid factor in the serum of a rheumatoid arthritis model mouse; can increase the content of short chain fatty acids (acetic acid, propionic acid, isobutyric acid, butyric acid and valeric acid) in the feces of a rheumatoid arthritis model mouse. The strain is a probiotic, has high safety, does not generate drug resistance, and does not cause adverse reaction of patients.
The invention also creatively discovers that the bifidobacterium animalis subsp Bifidobacterium animalis subsp.lactis BLa19 strain can be used for preventing, improving or treating the rheumatoid arthritis by being compounded with the lactobacillus casei Lactobacillus casei LC strain, has an effect which is remarkably superior to that of a single microbial inoculum or other compound formulas, and shows that the BLa19 strain and the LC89 strain have a synergistic effect on relieving the rheumatoid arthritis symptoms.
Detailed Description
In order to further describe the technical means adopted by the present invention and the effects thereof, the following describes the technical scheme of the present invention in combination with the preferred embodiments of the present invention, but the present invention is not limited to the scope of the embodiments.
The following related bifidobacterium animalis subspecies are Bifidobacterium animalis subsp.lactis BLa19 strains, the preservation unit is China general microbiological culture Collection center, the preservation number is CGMCC No.24028, the preservation date is 2021, 12 months and 2 days, and the preservation address is North West Lu No.1, 3 in the Korean region of Beijing city.
The lactobacillus casei is lactobacillus casei Lactobacillus casei LC strain, the preservation unit is China general microbiological culture Collection center, the preservation number is CGMCC No.15409, the preservation date is 2018, 3 months and 5 days, and the preservation address is North Chen West Lu No.1, 3 of the Korean region of Beijing city.
MRS solid medium as described below: weighing 10g of peptone, 10g of beef extract, 20g of glucose, 2g of sodium acetate, 5g of yeast powder, 2g of diammonium hydrogen citrate and K 2 PO 4 ·3H 2 O 2.6g、MgSO 4 ·7H 2 O 0.1g、MnSO 4 0.05g, 20g of agar and 0.5g of cysteine hydrochloride are dissolved by deionized water, 1mL of Tween 80 is added, the volume is fixed to 1L, and after sterilization and cooling, the mixture is poured into a sterilized culture dish for standby.
MRS liquid medium is as follows: weighing 10g of peptone, 10g of beef extract, 20g of glucose, 2g of sodium acetate, 5g of yeast powder, 2g of diammonium hydrogen citrate and K 2 PO 4 ·3H 2 O 2.6g、MgSO 4 ·7H 2 O 0.1g、MnSO 4 0.05g and 0.5g of cysteine hydrochloride are dissolved by deionized water, then 1mL of Tween 80 is added, the volume is fixed to 1L, and the sterilization and cooling are carried out for standby.
The following related bifidobacterium animalis subspecies gla 19 bacterial suspension: inoculating bifidobacterium animalis subspecies of milk BLa19 into MRS liquid culture medium, culturing at 37 ℃ for 18h for activation, and continuously activating for 2 times to obtain an activation solution; inoculating the activating solution into MRS liquid culture medium according to the inoculum size of 2% (v/v), and culturing at 37 ℃ for 18h to obtain bacterial solution; centrifuging the bacterial liquid for 10min at 8000g, and re-suspending the bacterial body by using PBS to obtain the bacterial liquid concentration which is diluted according to the requirement in the experiment.
The following related lactobacillus casei LC89 bacterial suspensions: inoculating lactobacillus casei LC89 into MRS liquid culture medium, culturing at 38deg.C for 18h for activation, and continuously activating for 2 times to obtain activating solution; inoculating the activating solution into MRS liquid culture medium according to the inoculum size of 2% (v/v), and culturing at 38deg.C for 18h to obtain bacterial solution; centrifuging the bacterial liquid at 8000g for 10min, and collecting supernatant, and filtering with 0.22 μm sterile filter membrane to obtain lactobacillus paracasei supernatant; and (3) re-suspending the bacterial cells by using PBS (phosphate buffered saline), and diluting the bacterial liquid concentration according to the requirement in the experiment.
Example 1
In this example, a bifidobacterium animalis subspecies is selected for relieving rheumatoid arthritis, and the steps are as follows:
(1) Infant faeces samples are selected, 10 times of gradient dilution is carried out by using physiological saline with the mass concentration of 0.9%, the samples are diluted 3 times, the samples are coated on an MRS solid culture medium (the culture medium contains an antibiotic mupirocin lithium salt which can inhibit most other strains except bifidobacterium, medicines are purchased from Haibo organisms), after culturing for 48 hours at 37 ℃, colonies with different forms are selected, streaked and purified on the surface of the MRS solid culture medium, single colonies are selected, expanded and cultured by using the MRS liquid culture medium at 37 ℃, and then the samples are preserved by using glycerol with the mass concentration of 30%.
(2) In vitro physiological property tests are carried out on the preserved single bacteria, and the method is specifically as follows:
A. evaluation of environmental resistance of strains to the gastrointestinal tract:
gastric juice is simulated manually: preparing 0.5% NaCl solution, adding 0.3% pepsin, adjusting pH to 2.5 with 1mol/L HCl, dissolving completely, and filtering with 0.22 μm microporous membrane for sterilization.
Manually simulating intestinal juice: preparing a 0.5% NaCl solution, adding 0.1% trypsin, adjusting the pH value to 8.0 by using 0.1mol/L NaOH, and filtering and sterilizing by using a 0.22 mu m microporous filter membrane after the solution is fully dissolved for later use.
Anaerobic culturing the preserved strain in artificial gastric juice and intestinal juice for 3 hours, taking digestion liquid of 0 hour and 3 hours for detecting viable count, and calculating the survival rate. Wherein, the survival rate (%) =a/b×100% of the strain, wherein a represents the number of viable bacteria (CFU/mL) of the strain for 0h, and B represents the number of viable bacteria (CFU/mL) of the strain for 3 h. Three replicates were run for each experiment.
B. Evaluation of HT-29 cell adhesion ability of the strain:
activating strains: inoculating the strain into anaerobic glass tube containing 0.1% L-cysteine hydrochloride MRS liquid culture medium according to 2% inoculum size, culturing at 37deg.C for 14 hr, centrifuging fermentation liquid, collecting thallus, washing with PBS for 3 times, suspending the thallus in DMEM culture solution without double antibody, and adjusting the concentration of the bacterial suspension to 10 8 CFU/mL。
HT-29 cell culture: in a cell culture flask, 5mL of DMEM complete medium (containing 10% fetal calf serum, 1% penicillin and streptomycin solution) was added to 5% CO 2 Incubation is carried out in a constant temperature incubator at 37 ℃, the culture solution is changed for 1 time every day, and after the cell state is good (70% -80% fusion), digestion and passage are carried out by using 0.2% digestive juice (pancreatin-EDTA).
Adhesion test: adjusting the concentration of digested HT-29 cells to 10 5 cell/mL, 1mL per well, inoculated into a 12-well cell culture plate, at 5% CO 2 Incubating in a concentration incubator until cells grow to a monolayer, washing twice with sterile PBS, digesting one well with pancreatin, and counting cells with a blood cell counting plate; respectively adding 1mL of the bacterial suspension and 1mL of the lactobacillus rhamnosus LGG bacterial suspension serving as a control bacterium into other holes, and adding 5% CO 2 After incubation in incubator at 37℃for 2h, cells were washed 5 times with sterile PBS to remove non-adherent bacterial suspension, and 0.2mL pancreas was added per wellThe enzyme-EDTA buffer solution digests the cells for 5min, 0.8mL PBS is added after the digestion is finished, the cells are uniformly blown, and the bacterial liquid is taken for dilution and viable count. Each experiment was performed in 3 replicates and the adhesion of the strain to HT-29 cells was examined by adhesion experiments.
C. Evaluation of the ability of the strain to inhibit pathogenic bacteria:
the oxford cup method is adopted, the strain is inoculated into an anaerobic glass tube containing 0.1 percent of L-cysteine hydrochloride MRS liquid culture medium according to 2 percent (V/V), and the strain is subjected to stationary culture at the constant temperature of 37 ℃ for 12 hours. Pathogenic strains such as escherichia coli, salmonella and staphylococcus aureus are respectively inoculated into a liquid beef extract peptone culture medium, cultured overnight at 37 ℃ with a constant temperature of 250rpm in a shaking table, and then pathogenic bacteria suspension is prepared. Cooling MRS solid culture medium to about 55deg.C, mixing with pathogenic bacteria suspension at a certain ratio to make the number of viable bacteria of the system be 10 6 CFU/mL, then rapidly pouring the culture medium into a flat plate in which an oxford cup is placed in advance, taking out the oxford cup after the culture medium is cooled and solidified, injecting 200 mu L of antagonistic strain bacteria liquid into each hole, lightly covering the flat plate, then placing the flat plate in a constant temperature incubator at 37 ℃, observing after proper time of culture, and measuring the diameter of a bacteriostasis ring by using a vernier caliper. Three replicates were run for each experiment.
By combining the above screening experiments, a strain with better gastrointestinal fluid tolerance (artificial simulation), HT-29 cell adhesion and bacteriostasis is screened out, and is named as bifidobacterium animalis subspecies lactis BLa19.
Example 2
In this example, the strains obtained by screening in example 1 were subjected to morphological identification and 16S rRNA molecular biology identification, as follows:
(1) Morphological identification:
the strain was inoculated in MRS solid medium, cultured at 37℃for 48 hours, and then observed under a microscope. The observation shows that the colony is white, semicircular, smooth and moist in surface and neat in edge.
(2) 16S rRNA molecular biology identification:
taking out the strain preserved at-80 deg.C, inoculating into a centrifuge tube filled with 20mL MRS liquid culture medium according to 2% ratio, culturing at 37 deg.C for 18h, centrifuging at 8000rpm for 10min, removing supernatant, and collecting thallus. Extracting genome of the strain, adding bacterial universal primer for PCR amplification, and delivering the amplified product to China academy of sciences microbiological study for sequencing and identification. The strain is subjected to sequencing analysis, and the 16S rRNA sequence of the strain is shown as SEQ ID No. 1. The sequences obtained by sequencing are subjected to nucleic acid sequence comparison in GeneBank, and the result shows that the strain is bifidobacterium animalis subspecies lactis.
SEQ ID No:1：
ACGGCTCCCCCCACAAGGGTCGGGCCACCGGCTTCGGGTGCTACCCACTTTCATGACTTGACGGGCGGTGTGTACAAGGCCCGGAACGCATTCACCGCGGCGTTGCTGATCCGCGATTACTAGCGACTCCGCCTTCACGCAGTCGAGTTGCAGACTGCGATCCGAACTGAGACCGGTTTTCAGCGATCCGCCCCACGTCACCGTGTCGCACCGCGTTGTACCGGCCATTGTAGCATGCGTGAAGCCCTGGACGTAAGGGGCATGATGATCTGACGTCATCCCCACCTTCCTCCGAGTTGACCCCGGCGGTCCCACATGAGTTCCCGGCATCACCCGCTGGCAACATGCGGCGAGGGTTGCGCTCGTTGCGGGACTTAACCCAACATCTCACGACACGAGCTGACGACGACCATGCACCACCTGTGAACCGGCCCCGAAGGGAAACCGTGTCTCCACGGCGATCCGGCACATTCAAGCCCAGGTAAGGTTCTTCGCGTTGCATCGAATTAATCCGCATGCTCCGCCGCTTGTGCGGGCCCCCGTCAATTTCTTTGAGTTTTAGCCTTGCGGCCGTACTCCCCAGGCGGGATGCTTAACGCGTTGGCTCCGACACGGGACCCGTGGAAAGGGCCCCACATCCAGCATCCACCGTTTACGGCGTGGACTACCAGGGTATCTAATCCTGTTCGCTCCCCACGCTTTCGCTCCTCACGTCAGTGACGGCCAGAGACCTGCCTTCGCCATTGGTGTTCTTCCCGATATCTACACATTCCACCGTTACACCGGGAATTCCAGTCTCCCCTACCGCACTCCAGCCCGCCCGTACCCGGCGCAGATCCACCGTTAGGCGATGGACTTTCACACCGGACGCGACGAACCGCCTACGAGCCCTTTACGCCCAATAAATCCGGATAACGCTCGCACCCTACGTATTACCGCGGCTGCTGGCACGTAGTTAGCCGGTGCTTATTCGAACAATCCACTCAACACGGCCGAAACCGTGCCTTGCCCTTGAACAAAAGCGGTTTACAACCCGAAGGCCTCCATCCCGCACGCGGCGTCGCTGCATCAGGCTTGCGCCCATTGTGCAATATTCCCCACTGCTGCCTCCCGTAGGAGTCTGGGCCGTATCTCAGTCCCAATGTGGCCGGTCACCCTCTCAGGCCGGCTACCCGTCAACGCCTTGGTGGGCCATCACCCCGCCAACAAGCTGATAGGACGCGACCCCATCCCATGCCGCAAAAGCATTTCCCACCCCACCATGCGATGGAGCGGAGCATCCGGTATTACCACCCGTTTCCAGGAGCTATTCCGGTGCACAGGGCAGGTTGGTCACGCATTACTCACCCGTTCGCCACTCTCACCCCGACAGCAAGCTGCCAGGGATCCCGTTCGACTG。
Based on the results of the 16S rRNA molecular biological identification and morphological identification of example 2, it was confirmed that the strain belongs to bifidobacterium animalis subspecies lactis, designated as bifidobacterium animalis subsp.lactis BLa19 strain.
Example 3
In this example, the culture conditions of bifidobacterium animalis subsp Bifidobacterium animalis subsp.
Inoculating Bifidobacterium animalis subspecies of Bla19 into MRS liquid culture medium, culturing at 20-45deg.C for 36 hr, and measuring OD of the culture solution by enzyme-labeling instrument at intervals 600 Numerical values. The results are shown in Table 1:
TABLE 1
The results show that BLa19 can reach the growth stabilization period after culturing for 18-24 hours at 30-37 ℃.
Example 4
This example demonstrates the therapeutic effect (body weight, toe swelling and clinical score) of bifidobacterium animalis subspecies gla 19 on rheumatoid arthritis mice, as follows:
(1) Healthy ICR male mice were selected for 60 animals, 8 weeks old, initial body weight of about 30g, and adapted to feed (free diet and drinking water) in animal houses (room temperature: 22-25 ℃ C. Humidity: 40-60%) for one week.
(2) And (3) molding: mixing chicken type II collagen with Complete Freund's Adjuvant (CFA) in equal volume, and emulsifying to obtain collagen emulsion. The emulsion is prepared by mixing and emulsifying in ice bath. Under aseptic conditions, the tail of 50 mice are injected subcutaneously with a dose of 0.1mL for the first time, and the mice are boosted by injecting the same injection with a dose of 0.1mL on day 21 after the first injection. Model mice were scored for arthritis 4 days apart after boost, 3 total times scored, and successfully model mice were screened.
(3) Grouping: then, 40 mice with no statistical significance for the difference in arthritis score were selected from the successfully modeled mice, and randomly divided into 4 groups (model group, group of Bla19 of Lactobacillus casei subspecies BLa19, LC89 group of Lactobacillus casei LC89, group of combined use of BLa19 and LC 89), 10 mice/group. Normal group, 10/group.
(4) Gastric lavage: (4.1) normal group: on day 2 after molding of the other groups of mice, each mouse was perfused with 0.5mL of physiological saline daily for 4 weeks. (4.2) model group: on day 2 after molding, each mouse was perfused with 0.5mL of physiological saline daily for 4 weeks. (4.3) group BLa 19: on day 2 after molding, each mouse was perfused with 1X 10g of stomach 0.5mL per day 10 CFU/mL of Bifidobacterium animalis subspecies Lactobacillus 19 broth. (4.4) LC89 group: on day 2 after molding, each mouse was perfused with 1X 10g of stomach 0.5mL per day 10 CFU/mL of Lactobacillus casei LC89 bacterial liquid. (4.5) combination group of Bla19 and LC 89: on day 2 after molding, each mouse was perfused with 1X 10g of stomach 0.4mL per day 10 CFU/mL of Bifidobacterium animalis subspecies Lactobacillus Bla19 bacterial liquid and 0.1mL concentration were 1X 10 10 CFU/mL of Lactobacillus casei LC89 bacterial liquid.
(5) Within 4 weeks of the mice' gavage period (0 weeks from completion of molding), the mice were observed weekly for feeding, and the weight of the mice, extent of toe swelling, and clinical scores were determined. The measurement results are shown in tables 2, 3 and 4.
TABLE 2
As can be seen from the data in table 2: within 4 weeks of the mice gavage, the mice of the other groups, except the normal group, were relatively slow-acting, had a slightly reduced food intake, and had a relatively reduced weight gain. During the period of mice lavage, the weight of the mice in the model group increases slowly, and even the weight of the mice in the first two weeks increases negatively; while the mice in the Bla19 group and the combination group had steadily increased in body weight. It is presumed that the administration of the BLa19 bacteria solution to rheumatoid arthritis mice resulted in some degree of relief of inflammation.
TABLE 3 Table 3
As can be seen from the data in table 3: the mice were gavaged for 4 weeks, the toe swelling of the mice in the model group was evident, and the toe of the mice in the model group was relieved to some extent compared with the toe of the mice in the model group BLa19 group and the combination group, which indicated that the inflammation was relieved to some extent by taking the BLa19 bacterial liquid to the rheumatoid arthritis mice.
TABLE 4 Table 4
As can be seen from the data in table 4: the gastric rheumatoid arthritis mice can be effectively reduced in arthritis score by using the BLa19 bacterial liquid, the LC89 bacterial liquid or the mixed bacterial liquid, the gastric 3-week arthritis score is highest, and the gastric 4-week arthritis score is reduced. It was found that bifidobacterium animalis subspecies lactis BLa19 can alleviate symptoms of rheumatoid arthritis.
Example 5
This example demonstrates the effect of bifidobacterium animalis subspecies gla 19 on Rheumatoid Factor (RF), IL-7 and PGLYRP-1 in serum of rheumatoid arthritis mice, as follows:
example 4 mice were sacrificed 4 weeks after gastric lavage, serum was taken, and Rheumatoid Factor (RF) was detected by nephelometry, and the content of interleukin 7 (IL-7) and peptidoglycan recognition protein 1 (PGLYRP-1) was determined by ELISA kit, as shown in table 5 (average presented in the table):
TABLE 5
As can be seen from the data in table 5: compared with the normal group, the serum RF level of the mice in the model group is obviously higher, and the BLa19 group and the combined group are obviously lower than the model group, which indicates that the gastric lavage BLa19 bacterial liquid of the mice can reduce the rheumatoid factors in the serum of the mice with rheumatoid arthritis. Compared with the normal group, the serum IL-7 level of the mice in the model group is obviously reduced, and the BLa19 group and the combined group are obviously higher than the model group, which indicates that the gastric lavage BLa19 bacterial liquid of the mice can call back the IL-7 level in the serum of the mice with rheumatoid arthritis. And compared with a model group, the BLa19 group and the combined group can reduce the PGLYRP-1 content in the serum of the rheumatoid arthritis mice.
The applicant states that the present invention is illustrated by the above examples as a bifidobacterium animalis subspecies gla 19 and its use in alleviating rheumatoid arthritis, but the invention is not limited to, i.e. it is not meant to be necessarily dependent on, the above examples. It should be apparent to those skilled in the art that any modification of the present invention, equivalent substitution of raw materials for the product of the present invention, addition of auxiliary components, selection of specific modes, etc., falls within the scope of the present invention and the scope of disclosure.
The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited to the specific details of the above embodiments, and various simple modifications can be made to the technical solution of the present invention within the scope of the technical concept of the present invention, and all the simple modifications belong to the protection scope of the present invention.
In addition, the specific features described in the above embodiments may be combined in any suitable manner, and in order to avoid unnecessary repetition, various possible combinations are not described further.
Claims (10)
1. Animal bifidobacterium subspecies of Lactobacillus capable of relieving rheumatoid arthritisBifidobacterium animalis subsp. lactis) BLa19, characterized in that said Bifidobacterium animalis subspecies of milk BLa19 capable of alleviating rheumatoid arthritis is designated Bifidobacterium animalis subspecies of milkBifidobacterium animalis subsp. lactisThe BLa19 strain has a preservation number of CGMCC No.24028 and a preservation date of 2021, 12 and 2.
2. Use of bifidobacterium animalis subspecies gla 19 capable of alleviating rheumatoid arthritis as claimed in claim 1 in the manufacture of a medicament for ameliorating or treating rheumatoid arthritis.
3. A probiotic agent for improving or treating rheumatoid arthritis, characterized in that the probiotic agent for improving or treating rheumatoid arthritis comprises the bifidobacterium animalis subspecies lactis of claim 1Bifidobacterium animalis subsp. lactisBla19 strain.
4. A probiotic agent for the amelioration or treatment of rheumatoid arthritis according to claim 3, characterized in that in said probiotic agent said bifidobacterium animalis subspecies lactisBifidobacterium animalis subsp. lactisThe viable count of BLa19 strain is not less than 1×10 8 CFU/mL or 1X 10 8 CFU/g。
5. A probiotic agent for the amelioration or treatment of rheumatoid arthritis according to claim 3, characterized in that said probiotic agent further comprises a protective agent and/or an auxiliary additive;
the protective agent comprises skimmed milk powder;
the auxiliary additive comprises any one or a combination of at least two of fructo-oligosaccharide, galacto-oligosaccharide, xylo-oligosaccharide, isomalto-oligosaccharide, soybean oligosaccharide, inulin, spirulina, arthrospira, coriolus versicolor polysaccharide, stachyose, polydextrose, alpha-lactalbumin or lactoferrin.
6. A composite probiotic for improving or treating rheumatoid arthritis, characterized in that the composite probiotic comprises the bifidobacterium animalis subspecies lactis of claim 1Bifidobacterium animalis subsp. lactisBla19 Strain and Lactobacillus casei [ (L-Lactobacillus casei.)Lactobacillus casei) LC89 strain; lactobacillus caseiLactobacillus caseiThe preservation number of the LC89 strain is CGMCC No.15409, and the preservation date is 2018, 3, 5.
7. The complex probiotic according to claim 6, characterized in that it is a bifidobacterium animalis subspecies lactis agent for improving or treating rheumatoid arthritisBifidobacterium animalis subsp. lactisBla19 strain and stemLactobacillus caseiLactobacillus caseiThe mass ratio of the LC89 strain is (2-4): 1.
8. The composite probiotic agent for the amelioration or treatment of rheumatoid arthritis according to claim 6, characterized in that it further comprises a protective agent and/or an auxiliary additive;
the protective agent comprises skimmed milk powder;
the auxiliary additive comprises any one or a combination of at least two of fructo-oligosaccharide, galacto-oligosaccharide, xylo-oligosaccharide, isomalto-oligosaccharide, soybean oligosaccharide, inulin, spirulina, arthrospira, coriolus versicolor polysaccharide, stachyose, polydextrose, alpha-lactalbumin or lactoferrin.
9. The method for culturing bifidobacterium animalis subspecies gla 19 capable of alleviating rheumatoid arthritis according to claim 1, wherein said method comprises inoculating bifidobacterium animalis subspecies gla 19 on MRS medium for culturing.
10. The method of culturing bifidobacterium animalis subspecies gla 19 capable of alleviating rheumatoid arthritis according to claim 9, wherein the temperature of the culturing is 30-37 ℃ and the time of the culturing is 18-24 h.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110669697A (en) * | 2019-10-31 | 2020-01-10 | 江苏微康生物科技有限公司 | Lactobacillus casei for high yield of short-chain fatty acid, culture method and application thereof |
| KR102271909B1 (en) * | 2020-06-24 | 2021-07-01 | 주식회사 바이오뱅크힐링 | Bifidobacterium animalis strain, and vesicles from thereof and anti-inflammation and anti-bacteria uses of thereof |
| CN114432346A (en) * | 2022-03-24 | 2022-05-06 | 金华银河生物科技有限公司 | Composite probiotic composition for treating hyperuricemia and gout and preparation method and application thereof |
| CN114470010A (en) * | 2022-02-07 | 2022-05-13 | 北京华元生物技术研究院 | New use of Bifidobacterium lactis BL-11 |
| CN114480229A (en) * | 2022-04-15 | 2022-05-13 | 微康益生菌(苏州)股份有限公司 | Bifidobacterium animalis subsp lactis strain WKB148 and product and application thereof |
| CN114728033A (en) * | 2019-09-20 | 2022-07-08 | 索法尔公司 | Composition based on bacterial strains and berry extract and its use as anti-inflammatory agent |
Family Cites Families (1)
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|---|---|---|---|---|
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-
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Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114728033A (en) * | 2019-09-20 | 2022-07-08 | 索法尔公司 | Composition based on bacterial strains and berry extract and its use as anti-inflammatory agent |
| CN110669697A (en) * | 2019-10-31 | 2020-01-10 | 江苏微康生物科技有限公司 | Lactobacillus casei for high yield of short-chain fatty acid, culture method and application thereof |
| KR102271909B1 (en) * | 2020-06-24 | 2021-07-01 | 주식회사 바이오뱅크힐링 | Bifidobacterium animalis strain, and vesicles from thereof and anti-inflammation and anti-bacteria uses of thereof |
| CN114470010A (en) * | 2022-02-07 | 2022-05-13 | 北京华元生物技术研究院 | New use of Bifidobacterium lactis BL-11 |
| CN114432346A (en) * | 2022-03-24 | 2022-05-06 | 金华银河生物科技有限公司 | Composite probiotic composition for treating hyperuricemia and gout and preparation method and application thereof |
| CN114480229A (en) * | 2022-04-15 | 2022-05-13 | 微康益生菌(苏州)股份有限公司 | Bifidobacterium animalis subsp lactis strain WKB148 and product and application thereof |
Non-Patent Citations (4)
| Title |
|---|
| Effects of Bifidobacterium animalis subsp. lactis HN019 on ligature-induced periodontitis in rats with experimental rheumatoid arthritis;R S Cardoso 等;Benef Microbes;第11卷(第1期);第33-46页 * |
| Mixture of probiotics reduces inflammatory biomarkers and improves the oxidative/nitrosative profile in people with rheumatoid arthritis;Ligia Aparecida Trintin Cannarella M.S 等;Nutrition;第89卷;第1-6页 * |
| Targeting Probiotics in Rheumatoid Arthritis;Simona Gabriela Bungau 等;Nutrients;13(10);第1-18页 * |
| 乳杆菌和双歧杆菌对类风湿性关节炎的缓解作用及机制研究;樊哲新;中国博士学位论文全文数据库（电子期刊）基础科学辑;20220115(第1期);A006-347 * |
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