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WO2025193919A1 - Procédés d'identification de chiens à risque supérieur de développement de maladie intestinale inflammatoire et traitements par intervention nutritionnelle - Google Patents

Procédés d'identification de chiens à risque supérieur de développement de maladie intestinale inflammatoire et traitements par intervention nutritionnelle

Info

Publication number
WO2025193919A1
WO2025193919A1 PCT/US2025/019723 US2025019723W WO2025193919A1 WO 2025193919 A1 WO2025193919 A1 WO 2025193919A1 US 2025019723 W US2025019723 W US 2025019723W WO 2025193919 A1 WO2025193919 A1 WO 2025193919A1
Authority
WO
WIPO (PCT)
Prior art keywords
canine
canine subject
abundance
susceptibility
inflammatory bowel
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/US2025/019723
Other languages
English (en)
Inventor
Jeffrey Allen BROCKMAN
Dayakar Venkata BADRI
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hills Pet Nutrition Inc
Original Assignee
Hills Pet Nutrition Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hills Pet Nutrition Inc filed Critical Hills Pet Nutrition Inc
Publication of WO2025193919A1 publication Critical patent/WO2025193919A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6888—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms
    • C12Q1/689—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for bacteria
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers

Definitions

  • a range from 1–5, includes specifically 1, 2, 3, 4 and 5, as well as subranges such as 2–5, 3– 5, 2–3, 2–4, 1–4, etc.
  • the term “about” when referring to a number means any number within a range of 15% of the number.
  • Embodiments include embodiments described herein with “about” modifying one or more numerical value. Further embodiments herein include removing one or more, or all, instances of “about” from embodiments herein described with “about” modifying one or more numerical value.
  • the abbreviations and symbols as used herein, unless indicated otherwise, take their ordinary meaning.
  • the abbreviation “wt.%” means percent by weight with respect to the composition.
  • the method comprises re- starting the feeding step if the test abundance is less than the control abundance upon a subsequent repeating step.
  • the control abundance is obtained from a table of Collinsellia intestinalis abundance. See Table 2, below, for a non-limiting example of a table from which Collinsellia intestinalis control abundance values may be obtained.
  • the control abundance is obtained for a canine of the same species as the canine subject.
  • the test abundance is determined by directly determining the number Collinsellia intestinalis in the canine subject.
  • the Collinsellia intestinalis test abundance is determined by culturing and/or dilution plating bacterial samples from fecal samples from the canine subject.
  • the culturing and/or dilution plating further comprises selecting for or assaying for Collinsellia intestinalis over other bacterial species.
  • the control abundance is determined by culturing and/or dilution plating a fecal sample from a canine lacking inflammatory bowel disease.
  • the culturing and/or dilution plating further comprises selecting for or assaying for Collinsellia intestinalis over other bacterial species.
  • the test abundance is determined by short read shotgun sequencing of DNA in a fecal sample from the canine subject to obtain reads matching Collinsellia intestinalis and a total number of identifiable reads.
  • the test abundance is the percentage of reads matching Collinsellia intestinalis relative to the total number of identifiable reads.
  • a determination of homozygous GG indicates lower susceptibility to inflammatory bowel disease for the canine subject relative to susceptibility for heterozygous GA or homozygous AA canines.
  • a determination of heterozygous GA indicates an intermediate susceptibility to inflammatory bowel disease for the canine subject between susceptibility for homozygous GG and homozygous AA canines.
  • a determination of homozygous AA indicates increased susceptibility to inflammatory bowel disease for the canine subject, above the susceptibility for either the homozygous GG or heterozygous GA canines.
  • a composition comprising a canine feed and at least about 2.5 wt.% quinoa.
  • the composition may comprise at least about 5 wt.% quinoa.
  • the composition may comprise at least about 10 wt.% quinoa.
  • the composition may comprise at least about 15 wt.% quinoa.
  • the composition may comprise at least about 20 wt.% quinoa.
  • the composition may comprise about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 wt.% quinoa, or an amount between any two of the foregoing.
  • the composition comprises quinoa in an amount as described above and at least one of from about 10 to about 20 wt.% fat crude, about 1 to about 5 wt.% fiber crude, from about 20 to about 30 wt.% protein crude, from about 2 to about 6 wt.% ash, and from about 45 to about 55 wt.% carbohydrate.
  • the composition comprises about 13 wt.% to about 14 wt.% crude fat, about 1.6 wt.% to about 1.7 wt.% fiber crude, about 22 wt.% to about 23.5 wt.% protein crude; about 4.6% to about 4.9% ash, about 6.8 wt.% to about 7.15 wt.% moisture, and about 48.6 wt.% to about 49.5 wt.% carbohydrate.
  • the composition comprises 13 wt.% to 14 wt.% crude fat, 1.6 wt.% to 1.7 wt.% fiber crude, 22 wt.% to 23.5 wt.% protein crude; 4.6% to 4.9% ash, 6.8 wt.% to 7.15 wt.% moisture, and 48.6 wt.% to 49.5 wt.% carbohydrate.
  • the composition comprises an amino acid content of at least one of alanine at about 1.5 to 1.7 wt.%, arginine at about 1 to about 1.4 wt.%, glycine at about 1.25 to about 1.6 wt.%, histidine at about 0.4 to about 0.6 wt.%, isoleucine at about 0.75 to about 1 wt.%, leucine at about 2.25 to about 2.5 wt.%, lysine at about 0.75 to about 1.1 wt.%, phenylalanine at about 1 to about 1.25 wt.%, proline at about 1.6 to about 2.0 wt.%, serine at about 0.9 to about 1.2 wt.%, threonine at about 0.3 to about 0.85 wt.%, tyrosine at about 0.6 to about 0.8 wt.%, valine at about 1 to about 1.2 wt.%, cystine at about 0.3 to about 0.6 wt.%, cystine at
  • the amino acid content may be adjusted depending on the amount of quinoa. See for example, FIG. 7B, which outlines varying amino acid content for 2.5, 5, 10, and 20 wt.% quinoa.
  • the composition comprises the components of one of the 2.5, 5, 10, or 20 wt.% quinoa diets listed Table 6A. In some embodiments, the composition comprises the components of one of the 2.5, 5, 10, or 20 wt.% quinoa diets listed in Table 6A at the amounts listed therein. In some embodiments, the composition comprises the components of one of the 2.5, 5, 10, or 20 wt.% quinoa diets listed in Table 6A at amounts within 15% of the amounts listed therein.
  • the composition comprises the amino acid content of one of the 2.5, 5, 10, or 20 wt.% quinoa diets listed in Table 6B at amounts listed therein. In some embodiments, the composition comprises the amino acid content of one of the 2.5, 5, 10, or 20 wt.% quinoa diets listed in Table 6B at amounts within 15% of the amounts listed therein. In some embodiments, the composition comprises the components of one of the 2.5, 5, 10, or 20 wt.% quinoa diets listed in Table 6A at the amounts listed therein and the amino acid content of Table 6B at the amounts listed therein.
  • the composition comprises the components of one of the 2.5, 5, 10, or 20 wt.% quinoa diets listed in Table 6A at amounts within 15% of the amounts listed therein and the amino acid content of Table 6B at amounts within 15% of the amounts listed therein.
  • Collinsellia intestinalis has been identified as one of the commensal bacteria in dogs, and it has been herein demonstrated that C. intestinalis is reduced over five-fold in a cohort of dogs clinically diagnosed with IBD.
  • a genetic locus in dogs is herein identified that significantly reduced the presence of C. intestinalis in the dog gut, putting dogs with this allele at higher risk for developing IBD.
  • a formula has been identified for a food that significantly increases the level of C.
  • Dog Cohort A cohort of 922 dogs were enrolled for this study. The subjects were client owned animals identified by approximately 20 veterinarian clinics across the United States. Inclusion criteria included being greater than 7 years of age and being of purebred status. No specific breeds were selected for. The cohort consisted of over 100 different dog breeds roughly representative of the breed demographics across the United States.
  • DNA extraction and metagenomic analysis DNA was extracted from the fecal samples collected from the 1000 dog cohort using QIAamp PowerFecal Pro DNA kit (Qiagen) followed by manufacturer instructions. Metagenomic analysis was performed at ComosID Inc., (Rockville, MD, USA) by using Illumina sequencing technology followed by their proprietary bioinformatics workflow for taxonomic profiling and abundance data. Each sample was sequenced at a depth of 6M reads. For taxonomic profiling, unassembled sequence reads are directly analyzed by CosmosID metagenomics software to reveal associated microbial composition.
  • DNA extraction for Genotyping DNA samples were collected from 922 dogs using the DNAGenotek saliva collection Kit. The collection sponge was placed inside the dog’s mouth in the pocket between the cheek and gum for 30 seconds to absorb saliva and cells then placed in the stabilizing lysis solution and stored at -80 degree C until DNA extraction. DNA was extracted by thawing the lysis solution and using a Qiagen DNA extraction kit as per manufacturer’s directions.
  • Genotyping Genome wide genotyping was performed using the Affymetrix Axiom Canine HD genotype array consisting of approximately 730,000 SNPs.
  • Genotyping was filtered using Plink (https://www.cog-genomics.org/plink2) for minor allele frequency greater than 5 percent (--maf 0.05), dropping individuals missing more than 10% of genotyping calls (--mind 0.1), and dropping genotypes missing more than 10% of calls (--geno 0.1). 157,498 SNPs were removed by filtering leaving 571,678, SNPs for downstream analysis. [0066] Phenotyping [0067] Animals in the cohort were thoroughly examined by a qualified veterinarian. Based on client interviews and clinical examination dogs with any clinical signs of inflammatory bowel disease were identified and diagnosed as such.
  • Microbiome analysis [0069] Total fecal DNA was extracted from frozen fecal samples by using MoBio PowerFecal DNA extraction kit followed by 16s rDNA amplicon sequencing using V3 and V4 hypervariable regions by employing MiSeq (Illumina) sequencing technology. The resulting sequences were demultiplexed by using MiSeq’s in-built “metagenomics” workflow to obtain FASTQ files. FASTQ files were processed by employing Mothur software to classify the sequence reads using Greengenes database followed by custom modifications. Those with less than 95% ubiquity were removed from the data analysis. The remaining 106 OTUs were included for analysis.
  • sequences can be matched to a database of all known genome sequences for microbes and the number of sequence reads matching a given organism quantified. By comparing the number of matched reads for one organism to the total number of identifiable reads one can calculate the relative level of that organism to the relative level of the other organisms in the database. The value for any given organism is expressed as a percentage of the total number of identifiable reads.
  • test diets were formulated based on Science Diet Canine Adult with inclusion of quinoa at different titers, 2.5 wt.%, 5 wt.%, 10 wt.% and 20 wt.% by reducing the levels of other grains in the control diet accordingly (Table 6A).
  • values of nutrient contents were corrected and equivalent with control diet (Science Diet Canine Adult). See FIGS. 7A and 7B and Tables 6A and 6B.
  • Control diet values are: 15.3 wt.% fat crude, 1.7 wt.% fiber crude, 6.7 wt.% moisture, 23.5 wt.% protein crude, 4.5 wt.% ash, and 48.13 wt.% carbohydrate.
  • a comparison of the Control diet and the Test diet with 2.5% quinoa is provided in Table 6C.
  • Table 6A Table 6A
  • each group was fed with four test diets (the test diets included quinoa at 2.5 wt.%, 5 wt.%, 10 wt.% and 20 wt.%) for another 14 days without a washout period.
  • the last group was fed with a control diet for another 14 days to measure the effect of the control diet over the study period as well as to check the feeding time effect.
  • Fecal samples were collected at the end of the pre-feeding period (14 th day) and at the end of the treatment period (28 th day).
  • the test diets (inclusion of quinoa at different titers) showed prebiotic effect by consistently inducing the abundance of beneficial bacteria Collinsella (FIGS.6 A, 6B, 6C, 6D) but not the control diet fed in the pre-feed and treatment phase (FIG.6E).
  • the differences in the levels of beneficial bacteria Collinsella were significant (p ⁇ 0.05) between the control diet and test diet (quinoa at different titers) but not significant between the control diet fed in the pre-feed and treatment phase.
  • the Collinsella abundance was compared between the treatments (quinoa at 2.5% wt., 5% wt., 10 wt.% and 20 wt.%) and this showed no significant differences.

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  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Organic Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Biotechnology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

L'invention concerne des méthodes d'identification d'un sujet canin sensible de développer une maladie intestinale inflammatoire, des méthodes de traitement ou de prévention d'une maladie intestinale inflammatoire chez un sujet canin, ainsi que des compositions utiles pour traiter ou prévenir une maladie intestinale inflammatoire chez un sujet canin.
PCT/US2025/019723 2024-03-14 2025-03-13 Procédés d'identification de chiens à risque supérieur de développement de maladie intestinale inflammatoire et traitements par intervention nutritionnelle Pending WO2025193919A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202463565363P 2024-03-14 2024-03-14
US63/565,363 2024-03-14

Publications (1)

Publication Number Publication Date
WO2025193919A1 true WO2025193919A1 (fr) 2025-09-18

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2025/019723 Pending WO2025193919A1 (fr) 2024-03-14 2025-03-13 Procédés d'identification de chiens à risque supérieur de développement de maladie intestinale inflammatoire et traitements par intervention nutritionnelle

Country Status (1)

Country Link
WO (1) WO2025193919A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015181361A1 (fr) * 2014-05-30 2015-12-03 Universitat Autonoma De Barcelona Puce à adn permettant de détecter les mutations des gènes du récepteur de type toll canin
WO2016038198A1 (fr) * 2014-09-12 2016-03-17 Swecure Ab Utilisation de collinsella pour le traitement d'une affection abdominale inflammatoire
WO2016108946A1 (fr) * 2014-12-29 2016-07-07 Hill's Pet Nutrition, Inc. Composition alimentaire et procédé d'utilisation
WO2020205911A1 (fr) * 2019-04-01 2020-10-08 Colorado State University Research Foundation Méthodes de diagnostic et de traitement d'une maladie intestinale inflammatoire chez des animaux de compagnie

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015181361A1 (fr) * 2014-05-30 2015-12-03 Universitat Autonoma De Barcelona Puce à adn permettant de détecter les mutations des gènes du récepteur de type toll canin
WO2016038198A1 (fr) * 2014-09-12 2016-03-17 Swecure Ab Utilisation de collinsella pour le traitement d'une affection abdominale inflammatoire
WO2016108946A1 (fr) * 2014-12-29 2016-07-07 Hill's Pet Nutrition, Inc. Composition alimentaire et procédé d'utilisation
WO2020205911A1 (fr) * 2019-04-01 2020-10-08 Colorado State University Research Foundation Méthodes de diagnostic et de traitement d'une maladie intestinale inflammatoire chez des animaux de compagnie

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KATHRANI A. ET AL: "Breed-independent toll-like receptor 5 polymorphisms show association with canine inflammatory bowel disease", TISSUE ANTIGENS., vol. 78, no. 2, 29 May 2011 (2011-05-29), DK, pages 94 - 101, XP093279716, ISSN: 0001-2815, Retrieved from the Internet <URL:https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1399-0039.2011.01707.x> DOI: 10.1111/j.1399-0039.2011.01707.x *
PEIRAVAN ATIYEH ET AL: "Genome-wide association studies of inflammatory bowel disease in German shepherd dogs", PLOS ONE, vol. 13, no. 7, 20 July 2018 (2018-07-20), US, pages e0200685, XP093279704, ISSN: 1932-6203, DOI: 10.1371/journal.pone.0200685 *

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