Probiotic compositions of p. hiranonis and methods

Abstract

Disclosed herein are compositions and methods of administering the compositions to animals to modulate gastrointestinal function and bile acid metabolism. The compositions include at least one canine-derived Peptacetobacter hiranonis strain and a pharmaceutically acceptable carrier. In certain embodiments, administration of the compositions is associated with increased conversion of primary bile acids to secondary bile acids and alterations in gastrointestinal microbial activity. Methods of preparing and formulating the compositions are also described.

Description

Attorney Docket No. 117693.00024PROBIOTIC COMPOSITIONS OF P. HIRANONIS AND METHODSBACKGROUND

[0001] Probiotics are live microorganisms that, when administered in adequate amounts, confer certain health benefits to the host by maintaining, improving, and / or restoring the gut microbiota. Although bile acid-modifying bacteria are present in the canine gastrointestinal tract, disruptions such as antibiotic exposure can result in prolonged impairment of specific bile acid conversion pathways that are not consistently or reliably restored by conventional probiotic formulations.SEQUENCE LISTING

[0002] This application contains a Sequence Listing which has been submitted electronically in ASCII text file format, entitled “117693.00024.xml” created on December 15, 2025, and having a size of 6 megabytes, which is hereby incorporated by reference in its entirety.SUMMARY

[0003] The present disclosure provides probiotic compositions comprising one or more canine-derived strains of Peptacetobacter hiranonis and methods of using such compositions to improve or restore bile acid metabolism and improve gastrointestinal health in companion animals, particularly dogs.

[0004] It has been discovered that dogs experiencing gastrointestinal dysbiosis, including dysbiosis following antibiotic treatment, frequently exhibit reduced abundance of P. hiranonis and impaired conversion of primary bile acids to secondary bile acids. Secondary' bile acids play an important role in maintaining intestinal homeostasis, including suppression of pathogenic taxa and regulation of host inflammatory responses. Prior to the present disclosure, there was no effective probiotic approach for restoring this specific metabolic function in dogs.

[0005] The present disclosure is based, in part, on the unexpected finding that administration of canine-derived P. hiranonis strains restores bile acid metabolic function in dogs by increasing conversion of cholic acid (CA) to deoxy cholic acid (DCA) and / or conversion of chenodeoxy cholic acid (CDCA) to lithocholic acid (LCA). This functional restoration occurs even in the absence of a significant increase in overall microbiome alpha diversity, demonstrating targeted recovery of a key metabolic pathway rather than nonspecific microbiome expansion.11106250992X3 XAMERICASAttorney Docket No. 117693.00024

[0006] In some embodiments, the probiotic composition comprises one or more strains of P. hiranonis having at least about 98% or at least 98.4% average nucleotide identity (ANI) to a strain deposited with the Belgian Coordinated Collections of Microorganisms (BCCM) under accession numbers LMG P-33640 (NCBI accession number: SAMN53834481), LMG P- 33642 (NCBI accession number: SAMN53834480), LMG P-33643(NCBI accession number: SAMN53834482), LMG P-33647(NCBI accession number: SAMN53835689), or LMG P- 33648(NCB1 accession number: SAMN53835690), or derivatives thereof. The disclosed strains possess bile acid deconjugation activity and bile acid 7a- and / or 7P-dehydroxylation pathway activity, enabling efficient conversion of primary bile acids to secondary bile acids.

[0007] Unexpectedly, the therapeutic benefit of administering P. hiranonis was found to depend on host-specific factors. Dogs treated within a defined period following antibiotic exposure exhibited significantly greater restoration of bile acid conversion efficiency than dogs treated at later time points, indicating a time-dependent window for optimal metabolic recovery. In addition, older dogs demonstrated greater increases in P. hiranonis abundance and greater improvements in bile acid conversion efficiency than younger dogs, revealing an age-dependent responsiveness that was not previously recognized.

[0008] Administration of the probiotic compositions described herein was further shown to improve stool quality and gastrointestinal symptoms in dogs with dysbiosis, while being safe and well-tolerated. In some embodiments, administration of the composition results in stable colonization or persistence of P. hiranonis following cessation of treatment.

[0009] In further aspects, the disclosure provides methods of treating gastrointestinal disorders, methods of increasing bile acid metabolism, and methods of restoring bile acid homeostasis in animals by administering a probiotic composition comprising one or more strains of P. hiranonis. The disclosure also provides methods of preparing such probiotic compositions, including culturing, isolating, and formulating one or more P. hiranonis strains with pharmaceutically acceptable carriers.BRIEF DESCRIPTION OF THE FIGURES

[0010] The drawings illustrate generally, by way of example, but not by way of limitation, various aspects discussed herein.

[0011] FIG. 1 shows a phylogenetic tree depicting the relationship between P. hiranonis and P. felis inferred from the core alignment of the genomes of six strains of Peptacetobacter felis isolated from cats, five strains Peptacetobacter hiranonis isolated fromAttorney Docket No. 117693.00024 dogs, the type strain for Peptacetobacter hiranonis isolated from humans, and the outgroup Paraclostridium bifermentans . Branch length and evolutionary distances are depicted.

[0012] FIG. 2 shows the transformation of primary bile acids into secondary bile acids across five bacterial strains over a 72-hour incubation period. The primary bile acids, cholic acid (CA) and chenodeoxycholic acid (CDCA), were transformed into secondary7bile acids, deoxy cholic acid (DCA) and lithocholic acid (LCA), respectively, by bacterial isolates ABCS0083 (SEQ ID NOs: 115-215), ABCS0500 (SEQ ID NOs: 1-114). ABCS0799 (SEQ ID NOs: 216-321), ABCS0846 (genetically identical to ABCS0847(SEQ ID NO: 323) and ABCS0849 (SEQ ID NO: 322). The concentrations of primary bile acids, including CA and CDCA, were measured at TO (before incubation), and their progressive reduction was monitored at T24, T48, and T72 hours. Correspondingly, the resulting secondary bile acids, DCA and LCA, were assessed at each of these time points.

[0013] FIG. 3 shows relative abundance of P. hiranonis in dogs having levels of <9.4% of P. hiranonis at the beginning (TO) and after 28 days of administration ofP. hiranonis ("Active") or administration of a placebo ("Placebo"). Dogs in the Active group showed a 3X greater increase in P. hiranonis (mean increase of 6.89%) over the initial timepoint compared to dogs in the Placebo group (mean increase of 2.27%) demonstrating that the probiotic can be delivered to the host effectively.

[0014] FIGS. 4A and 4B show efficiency of converting chenodeoxycholic acid (CDCA) to lithocholic acid (LCA), and efficiency of converting cholic acid (CA) to deoxy cholic acid (DCA), respectively, for dogs after 28 days of administration of P. hiranonis (“Active”) or administration of a placebo (“Placebo”), as measured by logio(LCA / CDCA) and logio(DCA / CDCA).

[0015] FIGS. 5A and 5B show, respectively, efficiency of converting chenodeoxycholic acid (CDCA) to lithocholic acid (LCA) as measured by logio(LCAZCDCA), and efficiency of converting cholic acid (CA) to deoxycholic acid (DCA) as measured by logio(DCAZCDCA), for dogs as a function of the number of days between their cessation of antibiotic treatment and their beginning probiotic treatment.

[0016] FIGS. 6A and 6B show, respectively, the change in relative abundance of P. hiranonis and the efficiency of converting chenodeoxycholic acid (CDCA) to lithocholic acid (LCA) as measured by logio(LCAZCDCA), for dogs as a function of their age in years.Attorney Docket No. 117693.00024DETAILED DESCRIPTIONOF ILLUSTRATIVE IMPLEMENTATIONS

[0017] Reference will now be made in detail to certain aspects of the disclosed subject matter, examples of which are illustrated in part in the accompanying drawings. While the disclosed subject matter will be described in conjunction with the enumerated claims, the exemplified subject matter is not intended to limit the claims to the disclosed subject matter.

[0018] This disclosure describes probiotic compositions isolated from dog (canine) hosts. The probiotic compositions may be administered to subjects to improve gut health of the subject. Generally, the probiotic compositions include one or more strains of Peptacetobacter hiranonis.

[0019] This disclosure describes identification and characterization of P. hiranonis isolated from dog hosts that may be used as a probiotic. First, whole genome sequencing was used to assess functional capabilities of P. hiranonis strains isolated from fecal samples of multiple dog donors. In-silico characterization identified phylogenetic and functional differences between strains.

[0020] Phylogenetic analysis of P. hiranonis strains

[0021] As described in Example 2 below, twelve Peptacetobacter hiranonis isolates were subjected to phylogenetic analysis together with the P. hiranonis type strain and representative non-canine Peptacetobacter species, including Peptacetobacter felis, as well as Paraclostridium bifermentans . resulting in the phylogeny as shown in FIG. 1. The twelve P. hiranonis isolates clustered into five groups, each of which is represented as a single branch in FIG. 1 identified by the name of the representative isolate and deposit. The group including isolates ABCS0005, ABCS0345, and ABCS0083 is represented by the microbes deposited with the Belgian Coordinated Collections of Microorganisms (BCCM) under the accession number LMG P-33640. The group including isolates ABCS0170 and ABCS0500 is represented by the microbes deposited with the BCCM under accession number LMG P- 33642. The group including isolates ABCS0798 and ABCS0799 is represented by microbes deposited with the BCCM under accession number LMG P-33643. The group including isolates ABCS0846 and ABCS0847 is represented by the microbes deposited with the BCCM under accession number LMG P-33647. The group including isolates ABCS0848, ABCS0849, and ABCS0979 is represented by the microbes deposited with the BCCM under accession number LMG P-33648. See Table A.TABLE AAttorney Docket No. 117693.00024

[0022] Primary to secondary bile acids conversion

[0023] All five model strains transformed primary bile acids into secondary bile acids over 72 hours in vitro. FIG. 2 shows the transformation of primary bile acids (CA, CDCA, and their conjugates) into secondary bile acids (DCA and LCA) by five bacterial strains (ABCS0083, ABCS0500, ABCS0799, ABCS0847, and ABCS0849) over a 72-hour incubation period. Primary and secondary bile acids were measured for each of two treatment groups ("Innoculated BA"), at the beginning of the experiment, when innoculants of cholic acid (CA) and chenodeoxy cholic acid (CDCA) were administered, and thereafter at 24 hours (T24), 48 hours (T48) and 72 hours (T72). The initial concentrations of primary bile acids, including cholic acid (CA) and chenodeoxy cholic acid (CDCA), are as shown at TO, before incubation, and the resulting concentrations of secondary bile acids, including deoxy cholic acid (DCA) and lithocholic acid (LCA), are as shown at T72 (after 72 hours).

[0024] The reduction in primary bile acid concentrations over 72 hours, together with the observed increases in secondary bile acids, suggests that the P. hiranonis strains described herein metabolized and transformed these bile acids. For example, cholic acid (CA) levels showed a marked decrease, particularly in samples inoculated with ABCS0083 and ABCS0799, indicating active bile acid metabolism. Similarly, conjugated bile acids, such as CDCA were significantly reduced, suggesting the ability of these strains to deconjugate and further transform primary bile acids into secondary bile acids. Meanwhile, Deoxy cholic acid (DCA), a secondary bile acid derived from CA, increased substantially in samples from 0 to 24, 48 and / or 72 hours, particularly with strains ABCS0847, ABCS0799, and ABCS0500, highlighting their efficiency in bile acid transformation. Lithocholic acid (LCA) levels also increased in specific strains, particularly ABCS0500 and ABCS0847.

[0025] As demonstrated by the studies described below in Example 4 (Tables 4 and 5), the P. hiranonis strains described herein converted primary bile acid CA to secondary bile acid DCA, within 72 hours or less, with percentages of conversion (conversion rates) rangingAttorney Docket No. 117693.00024 from 24.62 to 67.22, and DCA levels (production) ranging from 4. 14 to 42.18 ppm. As also demonstrated by the studies described below in Example 4 (Tables 4 and 5), the P. hiranonis strains described herein converted primary bile acid CDCA to secondary bile acid LCA, within 72 hours or less, with percentages of conversion (conversion rates) ranging from 8.98 to 51.33, albeit with low (.01-.25 ppm) or non-detectable LCA levels (production).

[0026] In summary, the P. hiranonis strains described herein metabolize (convert) primary bile acids CA and CDCA, including both conjugated and unconjugated forms, into secondary bile acids DCA and LCA, respectively. The P. hiranonis strains described herein convert CA bile acids, including both conjugated and unconjugated forms, into DCA bile acids with high efficiency, including conversion rates of greater than 24.0% for ABCS0083 (P-33640), greater than 50.0% for ABCS0500 (P-33642), greater than 41.0% for ABCS0799 (P-33643), greater than 62.0% for ABCS0847 (P-33647), and greater than 31.0% for ABCS0849 (P-33648).

[0027] Probiotic compositions

[0028] Thus, in one aspect, this disclosure describes probiotic compositions that generally include microbes from one or more strains of P. hiranonis. In some embodiments, the P. hiranonis are as deposited at BCCM under the accession number LMG P-33640, LMG P-33642, LMG P-33643, LMG P-33647 and / or LMG P-33648. In some embodiments, the P. hiranonis comprise derivatives of microbes deposited at BCCM under the accession number LMG P-33640. LMG P-33642, LMG P-33643, LMG P-33647 and / or LMG P-33648. In some embodiments, the P. hiranonis are microbes of a strain for which a representative sample was deposited with the BCCM under the accession number LMG P-33640, LMG P-33642, LMG P-33643, LMG P-33647 and / or LMG P-33648.

[0029] The probiotic composition can include microbes from two or more strains of P. hiranonis described in the preceding paragraph. The composition can include microbes from one or more genera other than Peptacetobacter. In an embodiment, the composition includes microbes from one or more of Faecalibacterium, Clostridrium, Saccharomyces (for example, S. boulardii), Bifidobacterium, Lactobacillus, Pediococcus. Propionibacterium, Streptococcus, and Bacillus. In an embodiment, the composition includes microbes of taxa other than Peptacetobacter that are recognized to be safe for administration, for example, QPS-recommended microorganisms (as identified, for example, by Zenodo.org at zenodo.org / records / 15827398).

[0030] In some embodiments, the strain or strains of P. hiranonis comprise(s) microbes having at least 98%, at least 98. 1%, at least 98.2%, at least 98.3%, at least 98.4%, atAttorney Docket No. 117693.00024 least 98.5%, at least 98.6%, at least 98.7%, at least 98.8%, at least 98.9%, at least 99.0%, at least 99. 1%, at least 99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9% average nucleotide identity (ANI) to microbes deposited with the Belgian Coordinated Collections of Microorganisms (BCCM) under the accession number LMG P-33640, LMG P-33642, LMG P-33643, LMG P-33647, or LMG P- 33648 and / or microbes of a strain for which a representative sample was deposited with the BCCM under the accession number LMG P-33640 (SEQ ID NOs: 115-215). LMG P-33642 (SEQ ID NOs: 1-114), LMG P-33643 (SEQ ID NOs: 216-321), LMG P-33647(SEQ ID NO: 323), or LMG P-33648 (SEQ ID NO: 322); and / or a strain for which a representative sample was deposited with the BCCM under the accession number LMG P-33640, LMG P-33642, LMG P-33643. LMG P-33647, or LMG P-33648 and / or derivatives thereof.

[0031] For purposes herein, Average Nucleotide Identity (ANI) refers to the mean nucleotide-level similarity' between homologous genomic regions shared by two microbial genomes. ANI values for the Peptacetobacter hiranonis strains described in this disclosure were calculated using ortholog genes clustering with OrthoMCL (Li, Christian J. Jr Stoeckert, and David S. Roos. 2003. ‘'OrthoMCL: Identification of Ortholog Groups for Eukary otic Genomes — Li et al. 13 (9): 2178 — Genome Research.” Genome Research 13 (9): 2178-89.), and computing ANI using methods described by (Contreras-Moreira, Bruno, and Pablo Vinuesa. 2013. GET HOMOLOGUES, a Versatile Software Package for Scalable and Robust Microbial Pangenome Analysis. Vol. 79. American Society for Microbiology; Vinuesa, Pablo, and Bruno Contreras-Moreira. 2015. ‘'Robust Identification of Orthologues and Paralogues for Microbial Pan-Genomics UsingGET HOMOLOGUES: A Case Study of PIncA / C Plasmids.” Methods in Molecular Biology 1231 : 203-32.).

[0032] As used herein, the term “derivative” with respect to an identified strain of P. hiranonis means a microbial isolate that originates from or is obtained by cultivation or genetic modification of that identified strain. In some embodiments, derivatives include spontaneous or induced mutants, natural variants, descendants, progeny, subcultures, and hybrids obtained therefrom, as well as isolates recovered from fecal or intestinal material of an animal administered the deposited strain. The term excludes non-viable metabolic products or purified biomolecules that are not living microbial cells.

[0033] When present in the probiotic composition, P. hiranonis microbes may be provided in an amount of from about 10 to about 1018colony forming units (CFUs). Thus, the probiotic composition can include a minimum of, for example, at least 10, at least IO2, at leastAttorney Docket No. 117693.00024IO3, at least 104, at least IO5, at least 106, at least 107, at least IO8, at least 109, at least IO10, at least IO11, at least 1012, at least IO13, at least 1014, at least IO15, at least 1016, at least 1017, or at least IO18CFU of P. hiranonis microbes. The probiotic composition can include a maximum of, for example, at most 102, at most IO3, at most 104, at most 105, at most 106, at most 107, at most 108, at most 109, at most IO10, at most 1011, at most 1012, at most IO13, at most 1014, at most 1015, at most 1016, at most 1017, or at most 1018CFU of P. hiranonis microbes. The probiotic composition can include an amount of P. hiranonis microbes expressed as a range having endpoints defined by any minimum amount of P. hiranonis microbes listed above and any maximum amount of P. hiranonis microbes listed above that is greater than the selected minimum amount. Thus, the probiotic composition can include, for example, from about 108CFU to about 109CFU of / ’, hiranonis microbes. The probiotic composition can include, for example, about 108CFU of / ’, hiranonis microbes. The probiotic composition can include, for example, about 109CFU ofP. hiranonis microbes. In some embodiments, the composition comprises 10A3 CFUs / ml to 10A10 CFUs / ml of the P. hiranonis microbes.

[0034] As used herein. “CFU” refers to the common term “colony forming unit,” a measure of viable cell numbers in CFU / mL. As used herein, “AFU” refers to “Active Fluorescent Units,” a measure of cells that uses flow cytometry to count viable microorganisms tagged with fluorescent markers by laser.

[0035] In an embodiment, the effective amount of P. hiranonis is 1 g / day of lyophilized P. hiranonis. In an embodiment, the effective amount of P. hiranonis is at least 1 x 10A7 or at least 1.4 x 10A7 AFUs per kilogram body weight of a dog being administered the composition.

[0036] The P. hiranonis microbes may be combined with a pharmaceutically acceptable carrier. As used herein, a “carrier” may be solid or liquid, and includes without limitation any solvent, dispersion medium, vehicle, coating, diluent, isotonic agent, absorption delaying agent, buffer, carrier solution, suspension, colloid, and the like.

[0037] Except insofar as any conventional media or agent is incompatible with the P. hiranonis microbes in the probiotic composition, its use in the probiotic compositions is contemplated. Supplementary active ingredients also can be incorporated into the probiotic compositions. As used herein, “pharmaceutically acceptable” refers to a material that is not biologically or otherwise undesirable, i.e., the material may be administered to an individual along with the P. hiranonis microbes without causing any undesirable biological effects or interacting in a deleterious manner with any of the other components of the probiotic composition in which it is contained.Attorney Docket No. 117693.00024

[0038] The probiotic composition may be formulated in a variety of forms adapted to a preferred route of administration. Thus, a composition can be administered via known routes including, for example, oral, parenteral (e.g., intradermal, transcutaneous, subcutaneous, intramuscular, intravenous, intraperitoneal, etc.), or topical (e.g., intranasal, intrapulmonary, intramammary, intravaginal, intrauterine, intradermal, transcutaneous, rectally, etc.). Thus, for example, the probiotic compositions described herein may be formulated for oral delivery.

[0039] The P. hiranonis probiotic composition may be provided in any suitable form including but not limited to a solid (e.g., a powder, capsule or tablet), a solution, a liquid suspension, a gel, an emulsion, a spray, an aerosol, or any form of mixture. The probiotic composition may be delivered in formulation with any pharmaceutically acceptable excipient, carrier, or vehicle. For example, the probiotic composition can include at least one / < hiranonis strain and a pharmaceutically acceptable excipient or carrier.

[0040] The probiotic composition as described herein can be delivered as a formulation in a conventional oral dosage form. Such a composition can include at least one P. hiranonis strain and a pharmaceutically acceptable carrier. Optionally, the probiotic composition can include at least one P. hiranonis strain and an enteric coating that reduces the extent to which the probiotic composition is released until after it exits the stomach of the subject to which the probiotic composition is administered.

[0041] The probiotic composition may be in the form of, for example, a gel, a liquid suspension, a cream, an ointment, an aerosol formulation, a non-aerosol spray, and the like.

[0042] The formulation may further include one or more additives including, but not limited to, a prebiotic, an adjuvant, a colorant, a fragrance, a flavoring, a thickener, and the like. Exemplary prebiotics include, but are not limited to, inulin, one or more mannose oligosaccharides (MOS), one or more fructo-oligosaccharides (FOS), one or more galactooligosaccharides (GOS), one or more disaccharides, one or more monosaccharides, one or more polyols, one or more sugar alcohols, oligofructose, or a combination of two or more prebiotics. Further, the formulation can involve one or more components being provided in a form or with an excipient that enhances stability of the product and / or survival through gastrointestinal tract if administered orally (e.g., an enteric coating, microencapsulation, etc.).

[0043] When present, a prebiotic may be provided in the probiotic composition at any desirable concentration. For example, the probiotic composition can include a prebiotic at a concentration of at least about 1 mg / ml, about 2 mg / ml, about 3 mg / ml, about 4 mg / ml, about 5 mg / ml, about 10 mg / ml, about 15 mg / ml, about 20 mg / ml, about 25 mg / ml, about 30Attorney Docket No. 117693.00024 mg / ml, about 35 mg / ml, about 40 mg / ml, about 45 mg / ml, about 50 mg / ml, about 55 mg / ml, about 60 mg / ml, about 65 mg / ml, about 70 mg / ml, about 75 mg / ml, about 80 mg / ml. about 85 mg / ml, about 90 mg / ml, about 95 mg / ml, about 100 mg / ml, about 110 mg / ml, about 125 mg / ml, about 130 mg / ml, about 140 mg / ml, or about 150 mg / ml. For example, the probiotic composition can include a prebiotic at a concentration of at most about 1 mg / ml, about 2 mg / ml, about 3 mg / ml, about 4 mg / ml, about 5 mg / ml, about 10 mg / ml, about 15 mg / ml. about 20 mg / ml, about 25 mg / ml, about 30 mg / ml, about 35 mg / ml, about 40 mg / ml, about 45 mg / ml, about 50 mg / ml, about 55 mg / ml, about 60 mg / ml, about 65 mg / ml, about 70 mg / ml, about 75 mg / ml, about 80 mg / ml, about 85 mg / ml, about 90 mg / ml, about 95 mg / ml, about 100 mg / ml, about 110 mg / ml, about 125 mg / ml, about 130 mg / ml, about 140 mg / ml, or about 150 mg / ml. For example, the probiotic composition can include a prebiotic at a concentration of about 1 mg / ml, about 2 mg / ml, about 3 mg / ml, about 4 mg / ml, about 5 mg / ml, about 10 mg / ml, about 15 mg / ml, about 20 mg / ml, about 25 mg / ml, about 30 mg / ml, about 35 mg / ml, about 40 mg / ml, about 45 mg / ml, about 50 mg / ml, about 55 mg / ml, about 60 mg / ml, about 65 mg / ml, about 70 mg / ml, about 75 mg / ml. about 80 mg / ml, about 85 mg / ml, about 90 mg / ml, about 95 mg / ml, about 100 mg / ml, about 110 mg / ml, about 125 mg / ml, about 130 mg / ml, about 140 mg / ml, or about 150 mg / ml.

[0044] A formulation may be conveniently presented in unit dosage form and may be prepared by methods well known in the art of pharmacy. Methods of preparing a composition with a pharmaceutically acceptable carrier include the step of bringing the P. hiranonis microbes into association with a carrier that constitutes one or more accessory ingredients. In general, a formulation may be prepared by uniformly and / or intimately bringing the active compound into association with a liquid carrier, a finely divided solid carrier, or both, and then, if necessary, shaping the product into the desired formulations. Thus, the probiotic composition may be formulated with a solid carrier, e g., for delivery as a powder or in a capsule such as, for example, a pet treat, a powder added to dry or wet food, an ingredient in a dry food, etc. The solid carrier can include microcrystalline cellulose, maltodextrin, or a similar earner. Alternatively, the probiotic composition may be formulated with a gel carrier or a liquid carrier, e.g., for delivery a gel or liquid added to dry or wet food, inclusion in a pet treat, inclusion in drinking water, etc. The probiotic composition may be formulated for sustained or delayed release.

[0045] In an embodiment, presented herein are probiotic compositions comprising at least one of the defined strains of P. hiranonis microbes, in an amount effective to improve one or more traits in a dog administered the composition. The one or more traits that areAttorney Docket No. 117693.00024 improved upon administration of the probiotic composition are selected from fecal quality and consistency, prevention of colonization of pathogenic microbes, and clearance of pathogenic microbes.

[0046] In an embodiment, administration of the probiotic composition reduced Streptococcus lutetiensis in dogs having initially high levels of S. lutetiensis (greater than 16%, 20%, 25%, 30% relative abundance) (GAM [3=19.98, p=0.04). In an embodiment, administration of the probiotic composition reduced Escherichia coli in dogs.

[0047] In an embodiment, presented herein are compositions comprising at least one of the defined strains of P. hiranonis microbes, in an amount effective to increase conversion of primary bile acids to secondary bile acids relative to an untreated control dog. The microbes can exhibit bile acid 7[3 dehydroxylation pathway activity and / or bile acid 7a dehydroxylation pathway activity. The composition can improve efficiency of conversion of chenodeoxy cholic acid to lithocholic acid, and / or efficiency of conversion of cholic acid to deoxy cholic acid. The conversion can be determined as a ratio of a measure of the secondary bile acid compared to a measure of the primary bile acid. The increase in conversion can correspond to a rise of at least 10% in conversion as measured in fecal samples.

[0048] The composition may be used in the preparation of a veterinary medicament for administering to an animal. Thus, this disclosure describes methods that involve administering to an animal a probiotic composition — e.g.. a veterinary medicament that includes the probiotic composition — that includes at least one strain of P. hiranonis. The probiotic composition may be administered to the animal to treat dysbiosis, an allergic condition such as a skin disorder, a gastrointestinal condition or disorder in the animal, and the like, and / or to increase bile acid metabolism in the animal.

[0049] In an embodiment, the composition is administered within 15 days, within 30 days, within 60 days, within 75 days, or within 90 days of administration of antibiotic to the dog treated. Generally, benefits of administration of the composition were higher the shorter the period of time between the antibiotic treatment and treatment with the composition. The composition is particularly beneficial when administered to dogs having levels of P. hiranonis in the gut that are less than those typically found in healthy dogs, for example, less than 9.4% or lower than the amount found in the 10thpercentile of healthy dogs.

[0050] The composition is beneficial for treatment of adult dogs, for example, dogs having an age of more than 1 year, more than 2 years, more than 3 years, or having an age in the range of I year to 12 years, 2 years to 12 years, or 3 years to 12 years. The composition is particularly beneficial for treatment of senior dogs. As used herein, “senior dog” refers to aAttorney Docket No. 117693.00024 dog that has reached approximately the final 33% of its expected lifespan, measured in years, based on breed, size, or population-average lifespan estimates. For example, for mediumsized dogs that have an expected lifespan of approximately 12 years, senior dogs would include dogs of about 8 years of age or older. In an embodiment, the composition is beneficial for dogs having an age of more than 6 years or having an age in the range of 6 years to 12 years.

[0051] “Treat” or variations thereof refer to reducing, limiting progression, ameliorating, or resolving, to any extent, the symptoms or signs related to a condition, including but not limited to a disorder. Thus, the methods of treatment described herein include administering an effective amount of the probiotic composition to a subj ect having, or at risk of having, a particular condition. In this aspect, an “effective amount” is an amount effective to reduce, limit progression, ameliorate, or resolve, to any extent, a symptom or clinical sign related to the condition.

[0052] “Dysbiosis” as used herein refers to any condition characterized by loss of microbial diversity, expansion of pathogenic taxa, and / or disruption of functional pathways. In veterinary science, dysbiosis has been associated with a wide array of GI and systemic conditions. Well-documented examples include: Chronic Enteropathies or IBD-like disease, chronic diarrhea, chronic vomiting, weight loss, Inflammatory Bowel Disease (lymphoplasmacytic. eosinophilic), antibiotic-associated gastrointestinal disturbance (GI signs that improve temporarily with antibiotics), acute diarrhea / acute GI upset, stress- associated gastrointestinal signs, colitis and large-bowel diarrhea, dietary indiscretion, parasite-triggered GI inflammation, Exocrine Pancreatic Insufficiency, diet-associated gastrointestinal disorders, chronic kidney disease, atopic dermatitis / allergic disease (gutskin axis), canine cognitive dysfunction (gut-brain axis), epilepsy (gut-brain axis), obesity and metabolic disease, endocrinopathies (e g., hypothyroidism), triaditis, and constipation / megacolon.

[0053] The method can include administering to the animal any probiotic composition described in this disclosure. The method can include administering to the animal a probiotic composition that includes at least one strain of P. hiranonis that possesses one or more of the following metabolic activities: bile acid 70 dehydroxylation pathway activity, bile acid 7a dehydroxylation pathway activity, convert cholic acid to deoxycholic acid, or convert chenodeoxy cholic acid to lithocholic acid.

[0054] In another aspect, this disclosure describes a method of preparing a probiotic composition. The method generally includes growing at least one strain of . hiranonisAttorney Docket No. 117693.00024 microbes in contact with a growth medium, isolating at least a portion of the P. hiranonis from the growth medium, and combining the isolated P. hiranonis microbes with a pharmaceutically acceptable carrier. Since the probiotic composition can include microbes from two or more strains of P. hiranonis, the method can involve any manner of preparing a probiotic composition that includes a combination of P. hiranonis strains. For example, separate P. hiranonis strains may be grown in separate cultures, separately isolated, then the separately isolated P. hiranonis strains may be combined with one another. In such an implementation, the culture medium used in the separate cultures may be the same or may be different. As another example, two or more strains of P. hiranonis may be grown together in a single culture, isolated from the culture medium together, then combined with the pharmaceutically acceptable carrier.

[0055] Microbes of a first strain of P. hiranonis can be grown in contact with a first growth medium, and microbes of a second strain of P. hiranonis can be grown in contact with a second growth medium. The first growth medium can be the same as or different than the second growth medium. At least a portion of the microbes of the first strain of P. hiranonis can be isolated from the first growth medium. At least a portion of the microbes of the second strain of P. hiranonis can be isolated from the second growth medium. In some embodiments, microbes of a first strain of P. hiranonis are grow n in contact with a first growth medium; microbes of a second strain ofP. hiranonis are grown in contact with a second growth medium; at least a portion of the microbes of the first strain of P. hiranonis are isolated from the first growth medium; and at least a portion of the microbes of the second strain of P. hiranonis are isolated from the second growth medium. In some embodiments, microbes of an isolated first strain of P. hiranonis are combined with microbes of an isolated second strain of P. hiranonis. and the combined microbes are then combined with a pharmaceutically acceptable carrier.

[0056] At least a portion of the microbes of an isolated first strain of P. hiranonis can be combined with a first pharmaceutically acceptable carrier to form a first intermediate composition. At least a portion of the microbes of an isolated second strain of P. hiranonis can be combined with a second pharmaceutically acceptable carrier to form a second intermediate composition. The first pharmaceutically acceptable carrier can be different than the second pharmaceutically acceptable carrier. In some embodiments, at least a portion of a first intermediate composition is combined with at least a portion of a second intermediate composition.Attorney Docket No. 117693.00024

[0057] In the preceding description and following claims, the term ‘‘and / or"’ means one or all of the listed elements or a combination of any two or more of the listed elements; the terms “comprises,” “comprising,” and variations thereof are to be construed as open ended — i.e., additional elements or steps are optional and may or may not be present; unless otherwise specified, “a,” “an,” “the,"’ and “at least one” are used interchangeably and mean one or more than one; and the recitations of numerical ranges by endpoints include all numbers subsumed within that range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3. 3.80, 4, 5, etc.).

[0058] As used herein, “have,” “has,” "‘having,” “include,” “includes,” "‘including,” “comprise,” “comprises,” “comprising” or the like are used in their open-ended inclusive sense, and generally mean “include, but not limited to,” “includes, but not limited to,” or “including, but not limited to.” Further, wherever implementations are described herein with the language "‘have,” “has,” “having,” "‘include,” “includes,” “including,” “comprise,” “comprises,” “comprising” and the like, otherwise analogous implementations described in terms of “consisting of” and / or “consisting essentially of’ are also provided. The term “consisting of’ means including, and limited to. that which follows the phrase “consisting of.” That is, “consisting of’ indicates that the listed elements are required or mandatory, and that no other elements may be present. The term “consisting essentially of’ indicates that any elements listed after the phrase are included, and that other elements than those listed may be included provided that those elements do not interfere with or contribute to the activity or action specified in the disclosure for the listed elements.

[0059] As used herein, the word “exemplary” means to serve as an illustrative example and should not be construed as preferred or advantageous over other implementations.

[0060] As used herein, the terms “preferred” and “preferably” refer to implementations of the invention that may afford certain benefits under certain circumstances. However, other implementations may also be preferred under the same or other circumstances. Furthermore, the recitation of one or more preferred implementations does not imply that other implementations are not useful and is not intended to exclude other implementations from the scope of the invention.

[0061] In the preceding description, particular implementations may be described in isolation for clarity7. Reference throughout this specification to “one implementation,” “an implementation,"’ “certain implementations,” “one or more implementations,” or “some implementations,” etc., means that a particular feature, configuration, composition, or characteristic described in connection with the implementation is included in at least oneAttorney Docket No. 117693.00024 implementation of the disclosure. Thus, the appearances of such phrases in various places throughout this specification are not necessarily referring to the same implementation of the disclosure. Furthermore, the particular features, configurations, compositions, or characteristics may be combined in any suitable manner in one or more implementations. Thus, features described in the context of one implementation may be combined with features described in the context of a different implementation except where the features are necessarily mutually exclusive.

[0062] In several places throughout the above description, guidance is provided through lists of examples, which examples can be used in various combinations. In each instance, the recited list serves only as a representative group and should not be interpreted as an exclusive list.

[0063] For any method disclosed herein that includes discrete steps, the steps may be performed in any feasible order. And, as appropriate, any combination of two or more steps may be performed simultaneously.

[0064] Unless otherwise indicated, all numbers expressing quantities of components, molecular weights, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless otherwise indicated to the contrary7, the numerical parameters set forth in the specification and claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary7rounding techniques.

[0065] Values expressed in a range format should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range w ere explicitly recited. For example, a range of “about 0.1% to about 5%” or “about 0.1% to 5%” should be interpreted to include not just about 0. 1% to about 5%, but also the individual values (e.g., 1%, 2%, 3%, and 4%) and the subranges (e.g., 0.1% to 0.5%, 1.1% to 2.2%, 3.3% to 4.4%) within the indicated range. The statement “about X to Y” has the same meaning as “about X to about Y,” unless indicated otherwise. Likewise, the statement “about X, Y, or about Z” has the same meaning as “about X, about Y, or about Z,” unless indicated otherwise.Attorney Docket No. 117693.00024

[0066] Unless expressly stated, ppm (parts per million), percentage, and ratios are on a by weight basis. Percentage on a by weight basis is also referred to as wt% or % (wt) below.

[0067] Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. All numerical values, however, inherently contain a range necessarily resulting from the standard deviation found in their respective testing measurements.

[0068] The complete disclosure of all patents, patent applications, and publications, and electronically available material (including, for instance, nucleotide sequence submissions in, e.g., GenBank and RefSeq, and amino acid sequence submissions in. e.g., SwissProt, PIR, PRF, PDB, and translations from annotated coding regions in GenBank and RefSeq) cited herein are incorporated by reference in their entirety. In the event that any inconsistency exists between the disclosure of the present application and the disclosure(s) of any document incorporated herein by reference, the disclosure of the present application shall govern. The foregoing detailed description and examples have been given for clarity of understanding only. No unnecessary limitations are to be understood therefrom. The invention is not limited to the exact details shown and described, for variations obvious to one skilled in the art will be included within the invention defined by the claims.

[0069] All headings are for the convenience of the reader and should not be used to limit the meaning of the text that follows the heading, unless so specified.EXAMPLES

[0070] The invention is further described in detail by reference to the following experimental examples. These examples are provided for purposes of illustration only and are not intended to be limiting unless otherwise specified. Thus, the invention should in no way be construed as being limited to the following examples, but rather should be construed to encompass any and all variations that become evident as a result of the teaching provided herein.

[0071] Example 1 - Culturing of Microbial Strains

[0072] During our culturomics workflow, we obtained our first isolate of P. hiranonis and investigated the culture conditions under which it had grown. We determined that the organism had been recovered using commercially available Brain Heart Infusion agar supplemented with horse blood and taurocholate (BHIY-HT). Recognizing the potentialAttorney Docket No. 117693.00024 selectivity of this medium for P. hiranonis, we adopted it as the basis for a targeted isolation strategy.

[0073] Using BHIY-HT, we established identical anaerobic culture conditions and systematically screened stool samples from a panel of healthy dog donors. This targeted approach proved effective: across all donor samples, we successfully isolated a total of 32 P. hiranonis isolates, representing 6 distinct strains.

[0074] These results highlight the utility of BH1Y -HT medium in selectively promoting the growth of P. hiranonis and allowing us to better characterize the species’ presence and diversity in domestic dog and cat populations.

[0075] Example 2 - Phylogenetic analysis

[0076] The genomes of dog-isolated strains of P. hiranonis were compared using core genome maximum likelihood phylogenetic inference. We used scapper (https: / / github.com / tseemann / scapper), which compares the genomes of interest to a reference, align the whole genome, identifies and trim the core genome, and the resulting alignment is used for phylogenetic reconstruction (RaxML Stamatakis, A., 2014.Bioinformatics 30(9): 1312-1313). The phylogenetic tree was rooted using the publicly available genome Paraclostridium bifermentans with midpoint rooting topology.

[0077] As shown in FIG. 1, the phylogenetic reconstruction resulted in tw elve Peptacetobacter spp. strains being grouped into two distinct clusters: one of which included six strains of P. felis collected from cats, the other of which included five strains of Peptacetobacter hiranonis isolated from dogs and the type strain for Peptacetobacter hiranonis isolated from humans. Branch length and evolutionary distances are depicted.

[0078] The phylogenetic tree of the whole genome revealed six different taxonomic branches, referred to here as strains, isolated from dogs. Different isolates for a taxonomic branch were often found to originate from a single host. See Table A, above.

[0079] The branch identified as ABCS0083 included three similar isolates, namely, ABCS0083, ABCS0005, and ABCS0345, and is represented by isolate ABCS0083, for which microbes were deposited with the Belgian Coordinated Collections of Microorganisms (BCCM) under the accession number LMG P-33640.

[0080] The branch identified as ABCS0500 included two similar isolates, namely, ABCS0170 and ABCS0500, and is represented by isolate ABCS0500, for which microbes were deposited w ith the Belgian Coordinated Collections of Microorganisms (BCCM) under the accession number LMG P-33642.Attorney Docket No. 117693.00024

[0081] The branch identified as ABCS0799 included two similar isolates, namely, ABCS0798 and ABCS0799. and is represented by isolate ABCS0799, for which microbes were deposited with the Belgian Coordinated Collections of Microorganisms (BCCM) under the accession number LMG P-33643.

[0082] The branch identified as ABCS0847 included two genetically identical isolates, namely, ABCS0846 and ABCS0847, and is represented by isolate ABCS0847, for which microbes were deposited with the Belgian Coordinated Collections of Microorganisms (BCCM) under the accession number LMG P-33647. We refer here to this branch as strain ABCS0847.

[0083] The branch identified as ABCS0849 included three similar isolates, namely, ABCS0848, ABCS0849. and ABCS0979. and is represented by isolate ABCS0849, for which microbes were deposited with the Belgian Coordinated Collections of Microorganisms (BCCM) under the accession number LMG P-33648.

[0084] Example 3 - ANI analysis

[0085] The Average Nucleotide Identity (ANI) of all five strains against all genomes was computed using clustered coding sequences generated by OrthoMCL (Li et al., 2003, Genome Res. 13:2178-2189). Table 2 shows that all the strains isolated from dogs, in pairwise comparisons to each other, have ANI greater than or equal to 95.24, and they cluster together as shown in FIG. 1.Table 2

[0086] Example 4 - Bile acid metabolism in silico analysis

[0087] Bile acid metabolism pathways were screened using gapseq (Zimmerman et al., 2021, Genome Biol 22:81). Table 3 summarizes the bile acid metabolism pathways ofAttorney Docket No. 117693.00024 each isolate by a specific pathway ID and associated with different processes involved in bile acid metabolism. These pathways include bile acid deconjugation (PWY-8135), bile acid 7p dehydroxylation (PWY-8134), bile acid 7a dehydroxylation (PWY-7754), and bile acid epimerization (PWY-6518). The presence (TRUE) or absence (FALSE) of these pathways in all the isolates is indicated in Table 3. All pathways, except bile acid epimerization, are prevalent across all samples. The 7p dehydroxylation and 7a dehydroxylation pathways are the most commonly observed, indicating these dehydroxylation processes are widespread across the isolates..Table 3 - Presence (TRUE) or absence (FALSE) of bile acid metabolism pathway genes in P. hiranonis isolates

[0088] Primary Bile Acid conversion rates as measured in vitro

[0089] To assess conversion of primary bile acids in the in vitro assay comparing the five different strains, we calculated conversion rates as follows: Conversion Rate=100 - ((initial - measured) / initial * 100).

[0090] The in vitro bile acid metabolism of Peptacetobacter hiranonis strains ABCS0500 (LMG P-33642), ABCS0083 (LMG P-33640), ABCS0799 (LMG P-33643).ABCS0849 (LMG P-33648), and ABCS0847 (LMG P-33647) reveals considerable variability in the conversion rates of primary bile acids (CA and CDCA) to secondary bile acids (DCA and LCA) (Table 4). Among the tested strains, ABCS0847 exhibited the highest efficiency in converting CA to DCA, with conversion rates above 62% across all time points, peaking at 67.22% at 24 hours. ABCS0500 also demonstrated strong conversion, increasing from 50.78% at 24 hours to 59.97% at 72 hours. In contrast, ABCS0083 and ABCS0799 showed moderate performance, with ABCS0799 experiencing a decline from 53.16% at 24Attorney Docket No. 117693.00024 hours to 41.66% at 72 hours. Strain ABCS0849 displayed lower CA-to-DCA conversion, starting at 41.18% at 24 hours and dropping to 31.68% by 72 hours.

[0091] The conversion of CDCA to LCA was generally less efficient but also showed variability among strains. ABCS0847 demonstrated substantial conversion, starting at 44.54% at 24 hours, decreasing to 28.94% at 48 hours, and then recovering to 38. 13% at 72 hours. ABCS0849 showed the highest peak conversion at 51.33% at 48 hours, though this decreased to 13.17% at 72 hours. Strains ABCS0083 and ABCS0799 maintained lower but relatively steady conversion rates of approximately 20%, while ABCS0500 exhibited more variable rates, peaking at 16.62% at 72 hours. These findings highlight strain-specific differences in bile acid metabolism, with ABCS0847 and ABCS0849 demonstrating significant capabilities in bile acid conversion compared to the other strains.Table 4. Primary bile acid conversion rates among strains in an in vitro assay conducted over 72 hours.

[0092] Secondary' Bile Acid Production

[0093] In terms of secondary bile acid production, DCA levels were notably higher than LCA levels across all strains (Table 5). Strains ABCS0500 and ABCS0847 produced the highest concentrations of DCA, with ABCS0500 maintaining levels between 37-44 ppm across all time points. ABCS0500 produced the highest DCA levels (44.39 ppm at 24 hours), while ABCS0847 exhibited the highest DCA production at 72 hours (42.18 ppm). StrainAttorney Docket No. 117693.00024ABCS0083 showed much lower DCA production, decreasing from 8.90 ppm at 24 hours to 4.14 ppm at 72 hours. ABCS0799 maintained stable DCA production at 24, 48 and 72 hours (26.99 ppm at 72 hours). LCA production was minimal or undetectable in most strains, with only ABCS0500 producing measurable amounts, albeit at very low levels (up to 0.25 ppm at 72 hours).

[0094] After 72 hours of incubation. ABCS0083 showed moderate reductions in primary bile acids, with a notable increase in DCA (4.14 ppm) but negligible LCA production, as indicated in Table 5. ABCS0500 exhibited steady primary bile acid reductions and the highest production of DCA at 72 hours (37.10 ppm), alongside increasing LCA levels (0.25 ppm). ABCS0799 demonstrated efficient transformation, with consistent DCA production (~26 ppm) and minimal LCA increases (0.02 ppm at 72 hours). ABCS0847 displayed significant reductions in CA and CDCA, with high production rates ofte DCA (42.18 ppm at 72 hours) but negligible production of LCA (albeitand moderate CDCA to LCA conversion (38.13%)). ABCS0849 showed reductions in primary bile acids and moderate DCA production (8.75 ppm), but negligible LCA formation.

[0095] These findings highlight strain-specific differences in bile acid metabolism, suggesting variability in the metabolic capabilities of P. hiranonis strains to convert and produce bile acids in vitro.Table 5. Secondary Bile Acid production among strains in an in vitro assay conducted over 72 hours.Attorney Docket No. 117693.00024

[0096] Beagle Safety Study Insights

[0097] Four colony beagle dogs (2 male and 2 female) were fed 2.5 g (IO10CFU) powder per day of fermented Peptacetobacter hiranonis strain ABCS0847 (P-33647) for 20 days with food. Fecal samples were collected prior to the start of the study (day -14 and day - 7) and after treatment (days 1, 2. 3, 8, 15, 20, and 27). The same sampling regimen was used for two beagles (one male and one female) that were not given any probiotic (1.25 g of nonfermented dry media components) and acted as the placebo group.

[0098] The probiotic composition was safe and well tolerated. No adverse effects were observed or reported for any of the 4 dogs receiving the probiotic composition. In addition, clinical / hematology markers remained normal.

[0099] Fecal samples were analyzed using full-length 16S rRNA gene PacBio sequencing for microbiome profiling. The fecal microbiomes of the dogs in the experimental treatment exhibited larger increases in the relative abundance P. hiranonis (A: 9.34%) compared to dogs in the placebo group (A: 6. 16%). Healthy beagle dogs receiving the P. hiranonis powder also tended to experience larger increases in the relative abundances of unclassified Fusobacterium (A: 2.33%), unclassified Blautia (A: 1.17%), Alloprevotella rava (A: 1.4%), Faecalibacterium prausnitzii (A: 2.04%), Ruminoccocus torques (A: 1.07%), and Catenibacterium mitsuokai (A: 0.85%) compared to dogs receiving the placebo. The aforementioned bacterial groups are common constituents of the microbiome of healthy dogs and perform functions that aid in host digestion of protein and carbohydrates.[000100] Example 5 - Field trial of dogs having dysbiosis administered a pharmaceutical composition disclosed herein[000101] Study Design: A double-blinded, placebo-controlled in-home study was conducted to evaluate the effectiveness of a probiotic composition comprising P. hiranonis described herein in improving gut health, particularly bile acid metabolism in companion animals with dysbiosis following antibiotic administration. We selected microbes derived from the isolate ABCS0847 (deposited as P-33647) for further development because they had the highest rates of conversion of CA to DCA of the strains tested (Table 4) and relatively high production of DCA (Table 5).[000102] Dogs were eligible if they had received a course of Metronidazole, Clavamox, Tylosin, or Doxycycline within the preceding 90 days and exhibited one or more gastrointestinal disturbances, including diarrhea, soft stool, or irregular bowel habits.Attorney Docket No. 117693.00024[000103] Seventy-two dogs completed the study (39 Active; 33 Placebo). The placebo consisted of 1 g microcrystalline cellulose per day. The active composition comprised 1 g / day of lyophilized P. hiranonis strain LMG P-33647 (approximately 5 x 109CFU / day) and was administered to the “Active” group by admixing with food for each of 28 consecutive days. Study timepoints were baseline (TO), day 14 (T14), day 28 (T28), and 15 days post-treatment (TPOST) (i.e., day 43). The cohort represented more than 30 breeds from four U.S. regions (West, Midwest, South, Northeast) and weights ranging from 10-36 kg. Approximately 44% presented with chronic enteropathy (CE)-like signs, 25% with food- or skin-related allergies, and 33% were clinically healthy. Approximately 42% had received a course of Clavamox, approximately 31% had received a course of Metronidazole, approximately 8% had received a course of Doxycycline, and approximately 19% had received a course of another antibiotic. [000104] Methods: Fecal samples collected at each timepoint were preserved for 16S rRNA sequencing and bile-acid quantification by liquid chromatography-mass spectrometry (LC-MS). Pet owners completed surveys at the study timepoints in which they noted, inter alia, stool consistency and frequency of loose stools, vomiting, and constipation, as well as overall tolerance. Microbiome analyses determined relative abundances of P. hiranonis and alpha-diversity indices (Shannon and Chaol). The Shannon Index metric can be used to measure microbiome diversity (Alpha Diversity ). The Shannon Index accounts for both abundance and evenness of each microbial species within the population.[000105] Bile-acid metabolic efficiency was evaluated as the ratio of secondary to primary bile acids, focusing on conversion of cholic acid (CA) to deoxy cholic acid (DCA) and chenodeoxy cholic acid (CDCA) to lithocholic acid (LCA).[000106] Results: The probiotic composition was safe and well tolerated. Only 7 dogs (4 Active, 3 Placebo) were withdrawn for unrelated reasons; no adverse effects were observed.[000107] As shown in FIG. 3, dogs having lower relative abundance of P. hiranonis in their gut (less than 9.4%) at the beginning of the study and receiving P. hiranonis (“Active”) exhibited a significant increase in P. hiranonis relative abundance compared to such dogs receiving the placebo (“Placebo”) (Wilcoxon W = 783, p = 0.043). In addition, dogs in the Active group show ed a 3X greater increase in P. hiranonis (mean increase of 6.89%) from the initial time point compared to dogs in the Placebo group (mean increase of 2.27%) (Wilcoxon test W= 816, p-value = 0.05). These findings suggest that a manufactured version of the probiotic can be delivered to the host effectively in a powder form delivered orally.Attorney Docket No. 117693.00024[000108] Approximately 46% of dogs receiving the active probiotic retained detectable P. hiranonis at the final time point (TPOST. 15 days following the final treatment), demonstrating stable colonization. Dogs with low or undetectable baseline levels showed the largest gains (Generalized Additive Model F=12.18. p=0.00136). The change in microbiome alpha-diversity (Chaol and Shannon) from TO to T28 did not differ significantly between groups (p > 0.6), indicating targeted restoration of functional taxa rather than overall expansion in bacterial diversity.[000109] As shown in FIGS. 4A and 4B, fecal metabolomic profiling revealed that probiotic-treated (“Active”) dogs converted primary’ to secondary' bile acids more efficiently than those in the placebo group (Wilcoxon W = 126, p = 0.03 for CA— >DCA; W = 187, p = 0.06 for CDCA^LCA). Conversion of CDCA to LCA improved significantly in the active group following administration of / < hiranonis for 28 days (GAM 0= -1.14, P=0.02, n=20 per group). Conversion of CA to DCA also improved significantly in the active group following administration of P. hiranonis for 28 days (GAM 0= -0.83, P=0.05, n=20 per group). The proportion of unconverted primary bile acids was significantly lower in the Active group (GAM 0 = 0.28, p = 0.045) providing further evidence that bile acid conversion capacity was enhanced in dogs receiving the probiotic.[000110] As shown in FIGS. 5A and 5B, dogs that received the probiotic within 60 days of antibiotic treatment displayed the highest conversion efficiencies. Improvements in bile acid conversion efficiency were negatively correlated with time after antibiotic exposure (GAM F = 6.07, p = 0.012 for CA^DCA; GAM F = 8.3, p = 0.014 for CDCA^LCA).[000111] As shown in FIG. 6A, the relative abundance of P. hiranonis increased significantly with age in the active group compared to baseline (Generalized Additive Model (GAM), P=0.03). More senior dogs, including dogs having an age of 6 years or more, were increasingly likely to experience a greater and / or positive change in abundance. As shown in FIG. 6B, older dogs converted CDCA to LCA more efficiently than younger dogs when given the probiotic (GAM F = 8.33, p = 0.014). More senior dogs, including dogs having an age of 6 years or more, were increasingly likely to have improved conversion of chenodeoxy cholic acid (CDCA) to lithocholic acid (LCA) after taking the probiotic for 28 days. Diarrhea symptoms were decreased in the Active group after 28 days of treatment, while constipation increased among placebo controls. Fecal consistency was improved in the Active group compared to Placebo after 28 days of treatment, as indicated by comparison of dogs having ideal fecal scores (3-4) (Fisher’s Exact Test, p<0.001, odds ration=0.17).Attorney Docket No. 117693.00024[000112] Body weight, diet, and general health status did not significantly influence these outcomes (p > 0.05). Body weight remained stable across groups.CLAUSES DESCRIBING THE INVENTION[000113] Clause 1. A composition comprising: microbes from at least one strain of P. hiranonis; and a pharmaceutically acceptable carrier; wherein the microbes comprise one or more of the following: microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the Belgian Coordinated Collections of Microorganisms (BCCM) under the accession number LMG P-33640 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P- 33640; microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33642 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33642; microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33643 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33643; microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33647 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33647; and microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33648 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P- 33648.[000114] Clause 2. The composition of clause 1, wherein the one strain of P. hiranonis is a strain for which a representative sample was deposited with the BCCM under the accession number LMG P-33647 or the accession number LMG P-33648.[000115] Clause 3. The composition of clause 1, wherein the one strain of P. hiranonis is a strain for which a representative sample was deposited with the BCCM under the accession number LMG P-33642, the accession number LMG P-33640, or the accession number LMG P-33643.[000116] Clause 4. The composition of clauses 1 or 2, wherein the microbes comprise: microbes having at least 98.4% average nucleotide identity (ANI) to microbes deposited with the BCCM under LMG P-33647 and / or microbes of a strain or isolate for which aAttorney Docket No. 117693.00024 representative sample was deposited with the BCCM under the accession number LMG P- 33647; or microbes having at least 98.4% average nucleotide identity (ANI) to microbes deposited with the BCCM under LMG P-33648 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33648.[000117] Clause 5. The composition of clauses 1 or 3, wherein the microbes comprise: microbes having at least 98.4% average nucleotide identity (ANI) to microbes deposited with the BCCM under LMG P-33640 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P- 33640; or microbes having at least 98.4% average nucleotide identity (ANI) to microbes deposited with the BCCM under LMG P-33642 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33642; or microbes having at least 98.4% average nucleotide identity (ANI) to microbes deposited with the BCCM under LMG P-33643 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33643.[000118] Clause 6. A composition comprising P. hiranonis, wherein the P. hiranonis is chosen from at least one deposited at BCCM under the accession number LMG P-33640, LMG P-33642, LMG P-33643, LMG P-33647 or LMG P-33648 and derivatives thereof.[000119] Clause 7. The composition of clause 6, wherein the P. hiranonis is chosen from at least one deposited at BCCM under the accession number LMG P-33640, LMG P- 33642, LMG P-33643 and derivatives thereof.[000120] Clause 8. The composition of clause 6, wherein the P. hiranonis is chosen from at least one deposited at BCCM under the accession number LMG P-33647 or LMG P- 33648 and derivatives thereof.[000121] Clause 9. A composition consisting of an effective amount of P. hiranonis, wherein the P. hiranonis is as deposited at BCCM under the accession number LMG P-33640, LMG P-33642, LMG P-33643, LMG P-33647 and / or LMG P-33648 and derivatives thereof, and at least one pharmaceutically acceptable carrier.[000122] Clause 10. The composition of clause 9, wherein the P. hiranonis is chosen from at least one deposited at BCCM under the accession number LMG P-33640, LMG P- 33642, and / or LMG P-33643 and derivatives thereof.Attorney Docket No. 117693.00024[000123] Clause 11. The composition of clause 9, wherein the P. hiranonis is chosen from at least one deposited at BCCM under the accession number LMG P-33647 and / or LMG P-33648 and derivatives thereof.[000124] Clause 12. The composition of any of clauses 9-11, wherein the effective amount of P. hiranonis is at least 1.4 x 10A7 AFUs per kilogram body weight of a dog being administered the composition.[000125] Clause 13. The composition of any of clauses 1, 6, and 9, wherein the composition comprises microbes having at least 98.4% average nucleotide identity (ANI) to microbes deposited with the BCCM under two or more of LMG P-33640, LMG P-33642, LMG P-33643. LMG P-33647 and LMG P-33648 and / or microbes of two or more strains for which a representative sample was deposited with the BCCM under the accession number LMG P-33640, LMG P-33642, LMG P-33643, LMG P-33647, and / or LMG P-33648.[000126] Clause 14. The composition of anyof clauses 1-13, wherein the composition is formulated for oral administration to a companion animal, and wherein optionally the formulation is a solid or a liquid.[000127] Clause 15. The composition of clause 14, wherein the companion animal is a dog.[000128] Clause 16. The composition of any of clauses 1-15, wherein the composition is formulated as a solid for oral administration by coating the composition partially or completely in an enteric coating that disintegrates only in the small intestine of a companion animal.[000129] Clause 17. The composition of any of clauses 1-16, wherein the composition comprises microbes from more than one strain of P. hiranonis.[000130] Clause 18. The composition of any of clauses 1-17 wherein the composition further comprises microbes from one or more of the following taxa:Faecali bacterium, Clostridium, Saccharomyces, Bifidobacterium, Lactobacillus, Pediococcus, Propionibacterium, Streptococcus, Bacillus, and Saccharomyces boulardii.[000131] Clause 19. The composition of any of clauses 1-18 for use in the preparation of a veterinary medicant for treating a gastrointestinal condition in an animal.[000132] Clause 20. A method of restoring bile acid metabolism in a dog, the method comprising: administering an effective amount of a composition comprising at least one canine-derived strain of P. hiranonis to the dog; wherein administration results in increased conversion of primary bile acids to secondary bile acids relative to untreated control dogs.Attorney Docket No. 117693.00024[000133] Clause 21. The method of clause 20, wherein: the probiotic composition is administered within 15 days, within 30 days, within 60 days, within 75 days, or within 90 days of administration of an antibiotic to the dog.[000134] Clause 22. The method of clauses 20 or 21, wherein the dog is a senior dog.[000135] Clause 23. The method of any of clauses 20-22, wherein the composition is the composition of any of clauses 1-18.[000136] Clause 24. A method of making a probiotic composition, the method comprising: growing microbes of at least one strain of P. hiranonis in contact w ith a growth medium; isolating P. hiranonis microbes from the growth medium; and combining at least a portion of the isolated P. hiranonis microbes with a pharmaceutically acceptable carrier; wherein the microbes are chosen from: microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the Belgian Coordinated Collections of Microorganisms (BCCM) under the accession number LMG P-33640; microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under LMG P-33642; microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under LMG P-33643; microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under LMG P-33647; and / or microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under LMG P-33648.[000137] Clause 25. The method of clause 24, wherein the probiotic composition comprises microbes of tw o or more strains of P. hiranonis that w ere grown in a single culture. [000138] Clause 26. The composition of any of clauses 1-5 and 9-12, wherein the pharmaceutically acceptable carrier comprises a solid, optionally maltodextrin or microcrystalline cellulose, or a liquid.[000139] Clause 27. The method of any of clauses 24-25, wherein the pharmaceutically acceptable carrier comprises a solid, optionally maltodextrin or microcrystalline cellulose, or a liquid.[000140] Clause 28. The method of clause 24, wherein: microbes of a first strain of P. hiranonis are grown in contact with a first grow th medium; microbes of a second strain of P. hiranonis are grow n in contact with a second grow th medium; at least a portion of the microbes of the first strain of P. hiranonis are isolated from the first growth medium; and at least a portion of the microbes of the second strain of P. hiranonis are isolated from the second growth medium.Attorney Docket No. 117693.00024[000141] Clause 29. The method of clause 28, wherein at least a portion of the microbes of the isolated first strain of P. hiranonis is combined with at least a portion of the microbes of the isolated second strain of P. hiranonis; and the combined microbes of the isolated first strain of P. hiranonis and the isolated second strain of P. hiranonis are combined with the pharmaceutically acceptable carrier.[000142] Clause 30. The method of clause 28, wherein at least a portion of the microbes of the isolated first strain of P. hiranonis are combined with a first pharmaceutically acceptable carrier to form a first intermediate composition; at least a portion of the microbes of the isolated second strain of P. hiranonis are combined with a second pharmaceutically acceptable carrier to form a second intermediate composition; and at least a portion of the first intermediate composition is combined with at least a portion of the second intermediate composition.[000143] Clause 31. The method of any of clauses 28-30, wherein the first grow th medium is different than the second grow th medium.[000144] Clause 32. The method of clause 30, wherein the first pharmaceutically acceptable carrier is different than the second pharmaceutically acceptable carrier.[000145] Clause 33. A method of treating dysbiosis in a dog, the method comprising: administering an effective amount of a probiotic composition comprising at least one strain of P. hiranonis and a pharmaceutically acceptable carrier; wherein, the administration of the effective amount of the probiotic composition increases conversion of primary bile acids to secondary bile acids relative to an untreated control animal.[000146] Clause 34. The method of clause 33, wherein the administration of the probiotic composition lessens diarrhea symptoms after 28 days of consecutive administration of the probiotic composition.[000147] Clause 35. The method of any of clauses 33-34, wherein the administration of the probiotic composition improves fecal consistency after 28 days of consecutive administration of the probiotic composition.[000148] Clause 36. A method of treating an allergic condition, optionally a skin- related allergy, in a dog, the method comprising: administering an effective amount of a probiotic composition comprising microbes of at least one strain of P. hiranonis and a pharmaceutically acceptable carrier; wherein, the administration of the effective amount of the probiotic composition increases conversion of primary bile acids to secondary bile acids relative to an untreated control dog.Attorney Docket No. 117693.00024[000149] Clause 37. The method of any of clauses 33-36, wherein the administration of the effective amount of the probiotic composition improves efficiency of conversion of chenodeoxy cholic acid to lithocholic acid, and / or efficiency of conversion of cholic acid to deoxy cholic acid.[000150] Clause 38. The method of any of clauses 33-37, wherein the conversion is determined as a ratio of a measure of the secondary bile acid compared to a measure of the primary bile acid.[000151] Clause 39. The method of any of clauses 33-38, where the increase in conversion corresponds to a rise of at least 10% in conversion as measured in fecal samples. [000152] Clause 40. The method of any of clauses 33-39, wherein the probiotic composition is administered within 30 days, within 60 days, or within 90 days of an antibiotic administration to the dogs treated.[000153] Clause 41. The method of any of clauses 33-40, wherein the levels of P. hiranonis in the gut of the dogs at the start of the treatment are less than 10% of relative abundance.[000154] Clause 42. The method of any of clauses 33-41, wherein the dog is a senior dog.[000155] Clause 43. The method of any of clauses 33-42, wherein the microbes exhibit bile acid 7 dehydroxylation pathway activity and / or bile acid 7a dehydroxylation pathway activity.[000156] Clause 44. The method of any of clauses 33-43, wherein the probiotic composition comprises: microbes of the strain for which a representative sample was deposited with the BCCM under the accession number LMG P-33640 having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33640 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33640; and / or microbes of the strain for which a representative sample was deposited with the BCCM under the accession number LMG P-33642 having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33642 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33642; and / or microbes of the strain for which a representative sample was deposited with the BCCM under the accession number LMG P- 33643 having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33643 and / or microbes of a strain or isolate forAttorney Docket No. 117693.00024 which a representative sample was deposited with the BCCM under the accession number LMG P-33643.[000157] Clause 45. The method of any of clauses 33-43, wherein the probiotic composition comprises: microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33647 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33647; and / or microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33648 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33648.[000158] Clause 46. The method of any of clauses 33-43, wherein the effective amount of the probiotic composition comprises at least 1.4 x 10A7 AFUs of the at least one strain of P. hiranonis per kilogram body weight of the dog.[000159] Clause 47. The method of any of clauses 33-46, wherein the pharmaceutically acceptable carrier comprises a solid or a liquid.[000160] Clause 48. The method of clause 47, wherein the pharmaceutically acceptable carrier comprises maltodextrin or microcrystalline cellulose.[000161] Clause 49. The method of any of clauses 33-48, wherein the probiotic composition is formulated for oral administration.[000162] Clause 50. The method of any of clauses 33-49, wherein the composition comprises microbes of P. hiranonis as deposited at BCCM under the accession number LMG P-33647 or LMG P-33648 and derivatives thereof.[000163] Clause 51. The method of any of clauses 33-49, wherein the composition comprises microbes of P. hiranonis as deposited at BCCM under the accession number LMG P-33640, LMGP-33642, or LMG P-33643 and derivatives thereof.[000164] Clause 52. The method of treatment, as in any of clauses 33-51, wherein the administration of the effective amount of the probiotic composition to the dog for at least 28 days consecutively increases relative abundance of the population of P. hiranonis in the gut of the subject dog upon treatment compared to dogs not administered the effective amount of the probiotic composition.[000165] Clause 53. The method of any of clauses 33-51, wherein the at least one strain of P. hiranonis continues to be retained in the gut of the dog at least 14 days after the probiotic was stopped.Attorney Docket No. 117693.00024Clause 54. A probiotic composition comprising: (a) purified and lyophilized P. hiranonis microbes comprising: microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33647 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33647; and / or microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33648 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33648; and / or microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33640 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33640; and / or microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33642 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33642; and / or microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33643 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33643; and (b) one or more pharmaceutically acceptable carriers suitable for dog administration; wherein the P. hiranonis microbes are in an amount effective to improve one or more traits in a dog administered the composition.[000166] Clause 55. The probiotic composition of clause 54, wherein: the purified and lyophilized P. hiranonis microbes comprise: microbes having at least 98.4% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33647 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33647; and / or microbes having at least 98.4% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33648 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33648.[000167] Clause 56. The probiotic composition of clause 55, wherein the microbes comprise nucleic acid sequences having at least 99.2% sequence identity to any of SEQ ID NOs: 1-114; 115-215; 216-321; 322; and 323.Attorney Docket No. 117693.00024[000168] Clause 57. The probiotic composition of clause 54, wherein: the purified and lyophilized P. hiranonis microbes comprise: microbes having at least 98.4% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33640 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33640; and / or microbes having at least 98.4% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33642 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33642; and / or microbes having at least 98.4% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33643 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33643;(b) one or more pharmaceutically acceptable carriers suitable for dog administration; wherein the P. hiranonis microbes are in an amount effective to improve one or more traits in a dog administered the composition.[000169] Clause 58. The probiotic composition of clause 57, wherein the microbes comprise nucleic acid sequences having at least 99.2% sequence identity to any of SEQ ID NOs: 1-114; 115-215; 216-321; 322; and 323.[000170] Clause 59. The probiotic composition of any of clauses 54-58. wherein the one or more traits that are improved upon administration of the probiotic composition are selected from fecal quality and consistency, prevention of colonization of pathogenic microbes, and clearance of pathogenic microbes.[000171] Clause 60. The probiotic composition of any of clauses 54-59. wherein the composition comprises 10A3 CFUs / ml to 10Al 0 CFUs / ml of the P. hiranonis microbes.[000172] Clause 61. The probiotic composition of any of clauses 54-60, wherein the carrier is chosen from microcrystalline cellulose or maltodextrin.[000173] Clause 62. The probiotic composition of any of clauses 54-61 wherein the composition is formulated as a solid for oral administration by coating the composition partially or completely in an enteric coating that disintegrates only in the small intestine of a companion animal.[000174] Clause 63. A composition comprising: at least one strain of a Peptacetobacter hiranonis species; and a pharmaceutically acceptable carrier, wherein the composition comprises microbes from one or more of the following P. hiranonis strains:Attorney Docket No. 117693.00024 microbes of the strain for which a representative sample was deposited with the Belgian Coordinated Collections of Microorganisms (BCCM) under the accession number LMG P- 33640 or a taxonomic variant thereof having at least 98% average nucleotide identity (ANI) to LMG P-33640; microbes of the strain for which a representative sample was deposited with the BCCM under the accession number LMG P-33642 having at least 98% average nucleotide identity (ANI) to LMG P-33642; microbes of the strain for which a representative sample was deposited with the BCCM under the accession number LMG P-33643 having at least 98% average nucleotide identity (ANI) to LMG P-33643; microbes of the strain for which a representative sample was deposited with the BCCM under the accession number LMG P-33647 having at least 98% average nucleotide identity (ANI) to LMG P-33647; and / or microbes of the strain for which a representative sample was deposited with the BCCM under the accession number LMG P-33648 having at least 98% average nucleotide identity’ (ANI) to LMG P-33648.[000175] Clause 64. The composition of clause 63, wherein the P. hiranonis microbe or microbes exhibit bile acid 7(3 dehydroxylation pathway activity and / or bile acid 7a dehydroxylation pathway activity.[000176] Clause 65. The composition of clauses 63 or 64, wherein the P. hiranonis microbes convert cholic acid to deoxy cholic acid and / or convert chenodeoxy cholic acid to lithocholic acid.[000177] Clause 66. The composition of any of clauses 63-65 for use in the preparation of a veterinary medicant for treating a gastrointestinal condition in an animal.[000178] Clause 67. A method of treating a gastrointestinal disorder in an animal, the method comprising administering to the animal the composition of any of clauses 63-65. [000179] Clause 68. A method of increasing bile acid metabolism in an animal, the method comprising administering to the animal the composition of any of clauses 63-65 and 67.[000180] Clause 69. The method of any of clauses 67-68 wherein the animal is a dog.[000181] Clause 70. A probiotic composition wherein the microbes comprise nucleic acid sequences having at least 99.2% sequence identity to any of SEQ ID NOs: 1-114. [000182] Clause 71. A probiotic composition wherein the microbes comprise nucleic acid sequences having at least 99.2% sequence identity to any of SEQ ID NOs: 115- 215.[000183] Clause 72. A probiotic composition wherein the microbes comprise nucleic acid sequences having at least 99.2% sequence identity to any of SEQ ID NOs: 216-231.Attorney Docket No. 117693.00024[000184] Clause 73. A probiotic composition wherein the microbes comprise nucleic acid sequences having at least 99.2% sequence identity to any of SEQ ID NO: 322.[000185] Clause 74. A probiotic composition wherein the microbes comprise nucleic acid sequences having at least 99.2% sequence identity to any of SEQ ID NO:323.[000186] Clause 75. A method of treating a gastrointestinal condition in an animal, the method comprising administering to the animal the microbial composition of any of clauses 1-18, 54-65, and 70-74.[000187] Clause 76. A method of increasing bile acid metabolism in an animal, the method comprising administering to the animal the composition of any of clauses 1-18, 54- 65, and 70-74.[000188] Clause 77. A method of treating dysbiosis in an animal, the method comprising administering to the animal the composition of any of clauses 1-18, 54-65, and 70-74.[000189] Clause 78. The method of any of clauses 75-77, wherein the animal is a dog.

Claims

Attorney Docket No. 117693.00024CLAIMSWhat is claimed is:

1. A composition comprising: microbes from at least one strain of P. hiranonis,' and a pharmaceutically acceptable carrier; wherein the microbes comprise one or more of the following: microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the Belgian Coordinated Collections of Microorganisms (BCCM) under the accession number LMG P-33640 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33640: microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33642 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33642; microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33643 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33643; microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33647 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33647; and microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33648 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33648.

2. The composition of claim 1, wherein the one strain of P. hiranonis is a strain for which a representative sample was deposited with the BCCM under the accession number LMG P-33647 or the accession number LMG P-33648.Attorney Docket No. 117693.000243. The composition of claim 1, wherein the one strain of / *, hiranonis is a strain for which a representative sample was deposited with the BCCM under the accession number LMG P-33642, the accession number LMG P-33640, or the accession number LMG P-33643.

4. The composition of claim 1 or 2. wherein the microbes comprise: microbes having at least 98.4% average nucleotide identity (ANI) to microbes deposited with the BCCM under LMG P-33647 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33647; or microbes having at least 98.4% average nucleotide identity (ANI) to microbes deposited with the BCCM under LMG P-33648 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33648.

5. The composition of claim 1 or 3, wherein the microbes comprise: microbes having at least 98.4% average nucleotide identity (ANI) to microbes deposited with the BCCM under LMG P-33640 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33640; or microbes having at least 98.4% average nucleotide identity (ANI) to microbes deposited with the BCCM under LMG P-33642 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33642; or microbes having at least 98.4% average nucleotide identity (ANI) to microbes deposited with the BCCM under LMG P-33643 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33643.

6. A composition comprising P. hiranonis, wherein the P. hiranonis is chosen from at least one deposited at BCCM under the accession number LMG P-33640, LMG P- 33642, LMG P-33643, LMG P-33647 or LMG P-33648 and derivatives thereof.Attorney Docket No. 117693.000247. The composition of claim 6, wherein the P. hiranonis is chosen from at least one deposited at BCCM under the accession number LMG P-33640, LMG P-33642, LMG P-33643 and derivatives thereof.

8. The composition of claim 6, wherein the P. hiranonis is chosen from at least one deposited at BCCM under the accession number LMG P-33647 or LMG P-33648 and derivatives thereof.

9. A composition consisting of an effective amount of P. hiranonis, wherein the P. hiranonis is as deposited at BCCM under the accession number LMG P-33640, LMG P-33642, LMG P-33643. LMG P-33647 and / or LMG P-33648 and derivatives thereof, and at least one pharmaceutically acceptable carrier.

10. The composition of claim 9, wherein the P. hiranonis is chosen from at least one deposited at BCCM under the accession number LMG P-33640, LMG P-33642, and / or LMG P-33643 and derivatives thereof.

11. The composition of claim 9, wherein the P. hiranonis is chosen from at least one deposited at BCCM under the accession number LMG P-33647 and / or LMG P-33648 and derivatives thereof.

12. The composition of any of claims 9-11, wherein the effective amount of P. hiranonis is at least 1.4 x 10A7 AFUs per kilogram body weight of a dog being administered the composition.

13. The composition of any of claims 1, 6, and 9, wherein the composition comprises microbes having at least 98.4% average nucleotide identity (ANI) to microbes deposited with the BCCM under two or more of LMG P-33640, LMG P-33642, LMG P-33643, LMG P-33647 and LMG P-33648 and / or microbes of two or more strains for which a representative sample was deposited with the BCCM under the accession number LMG P-33640, LMG P-33642, LMG P-33643, LMG P-33647, and / or LMG P-33648.Attorney Docket No. 117693.0002414. The composition of any of claims 1-13, wherein the composition is formulated for oral administration to a companion animal, and wherein optionally the formulation is a solid or a liquid.

15. The composition of claim 14, wherein the companion animal is a dog.

16. The composition of any of claims 1-15 wherein the composition is formulated as a solid for oral administration by coating the composition partially or completely in an enteric coating that disintegrates only in the small intestine of a companion animal.

17. The composition of any of claims 1-16, wherein the composition comprises microbes from more than one strain of P. hiranonis.

18. The composition of any of claims 1-17 wherein the composition further comprises microbes from one or more of the following taxa: Faecalibacterium, Clostridium, Saccharomyces, Bifidobacterium, Lactobacillus, Pediococcus, Propionibacterium, Streptococcus, Bacillus, and Saccharomyces boulardii.

19. The composition of any of claims 1-18 for use in the preparation of a veterinary’ medicant for treating a gastrointestinal condition in an animal.

20. A method of restoring bile acid metabolism in a dog, the method comprising: administering an effective amount of a composition comprising at least one canine-derived strain of P. hiranonis to the dog; wherein administration results in increased conversion of primary bile acids to secondary bile acids relative to untreated control dogs.

21. The method of claim 20, wherein: the probiotic composition is administered within 15 days, within 30 days, within 60 days, within 75 days, or within 90 days of administration of an antibiotic to the dog.

22. The method of claim 20 or claim 21, wherein the dog is a senior dog.Attorney Docket No. 117693.0002423. The method of any of claims 20-22, wherein the composition is the composition of any of claims 1-18.

24. A method of making a probiotic composition, the method comprising: growing microbes of at least one strain of P. hiranonis in contact with a growth medium; isolating P. hiranonis microbes from the growth medium; and combining at least a portion of the isolated P. hiranonis microbes with a pharmaceutically acceptable carrier; wherein the microbes are chosen from: microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the Belgian Coordinated Collections of Microorganisms (BCCM) under the accession number LMG P-33640; microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under LMG P-33642: microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under LMG P-33643; microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under LMG P-33647; and / or microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under LMG P-33648.

25. The method of claim 24, wherein the probiotic composition comprises microbes of two or more strains of P. hiranonis that were grown in a single culture.

26. The composition of any of claims 1-5 and 9-12, wherein the pharmaceutically acceptable carrier comprises a solid, optionally maltodextrin or microcrystalline cellulose, or a liquid.

27. The method of any of claims 24-25, wherein the pharmaceutically acceptable carrier comprises a solid, optionally maltodextrin or microcrystalline cellulose, or a liquid.

28. The method of claim 24, wherein:Attorney Docket No. 117693.00024 microbes of a first strain of P. hiranonis are grown in contact with a first growth medium; microbes of a second strain of P. hiranonis are grown in contact with a second growth medium; at least a portion of the microbes of the first strain of P. hiranonis are isolated from the first growth medium; and at least a portion of the microbes of the second strain of P. hiranonis are isolated from the second growth medium.

29. The method of claim 28, wherein at least a portion of the microbes of the isolated first strain of P. hiranonis is combined with at least a portion of the microbes of the isolated second strain of P. hiranonis,' and the combined microbes of the isolated first strain of P. hiranonis and the isolated second strain of P. hiranonis are combined with the pharmaceutically acceptable carrier.

30. The method of claim 28, wherein at least a portion of the microbes of the isolated first strain of P. hiranonis are combined with a first pharmaceutically acceptable carrier to form a first intermediate composition; at least a portion of the microbes of the isolated second strain of P. hiranonis are combined with a second pharmaceutically acceptable carrier to form a second intermediate composition; and at least a portion of the first intermediate composition is combined with at least a portion of the second intermediate composition.

31. The method of any of claims 28-30, wherein the first growth medium is different than the second growth medium.

32. The method of claim 30, wherein the first pharmaceutically acceptable carrier is different than the second pharmaceutically acceptable carrier.

33. A method of treating dysbiosis in a dog, the method comprising:Attorney Docket No. 117693.00024 administering an effective amount of a probiotic composition comprising at least one strain of P. hiranonis and a pharmaceutically acceptable carrier; wherein, the administration of the effective amount of the probiotic composition increases conversion of primary bile acids to secondary bile acids relative to an untreated control animal.

34. The method of claim 33, wherein the administration of the probiotic composition lessens diarrhea symptoms after 28 days of consecutive administration of the probiotic composition.

35. The method of any of claims 33-34, wherein the administration of the probiotic composition improves fecal consistency after 28 days of consecutive administration of the probiotic composition.

36. A method of treating an allergic condition, optionally a skin-related allergy, in a dog. the method comprising: administering an effective amount of a probiotic composition comprising microbes of at least one strain of P. hiranonis and a pharmaceutically acceptable carrier; wherein, the administration of the effective amount of the probiotic composition increases conversion of primary bile acids to secondary bile acids relative to an untreated control dog.

37. The method of any of claims 33-36, wherein the administration of the effective amount of the probiotic composition improves efficiency of conversion of chenodeoxy cholic acid to lithocholic acid, and / or efficiency of conversion of cholic acid to deoxycholic acid.

38. The method of any of claims 33-37, wherein the conversion is determined as a ratio of a measure of the secondary bile acid compared to a measure of the primary bile acid.

39. The method of any of claims 33-38, where the increase in conversion corresponds to a rise of at least 10% in conversion as measured in fecal samples.Attorney Docket No. 117693.0002440. The method of any of claims 33-39, wherein the probiotic composition is administered within 30 days, within 60 days, or within 90 days of an antibiotic administration to the dogs treated.

41. The method of any of claims 33-40, wherein the levels of / *, hiranonis in the gut of the dogs at the start of the treatment are less than 10% of relative abundance.

42. The method of any of claims 33-41, wherein the dog is a senior dog.

43. The method of any of claims 33-42, wherein the microbes exhibit bile acid 70 dehydroxylation pathway activity and / or bile acid 7a dehydroxylation pathway activity.

44. The method of any of claims 33-43, wherein the probiotic composition comprises: microbes of the strain for which a representative sample was deposited with the BCCM under the accession number LMG P-33640 having at least 98% average nucleotide identity7(ANI) to microbes deposited with the BCCM under the accession number LMG P-33640 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33640; and / or microbes of the strain for which a representative sample was deposited with the BCCM under the accession number LMG P-33642 having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33642 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33642; and / or microbes of the strain for which a representative sample was deposited with the BCCM under the accession number LMG P-33643 having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33643 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33643.Attorney Docket No. 117693.0002445. The method of any of claims 33-43, wherein the probiotic composition comprises: microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33647 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33647; and / or microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33648 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33648.

46. The method of any of claims 33-43, wherein the effective amount of the probiotic composition comprises at least 1.4 x 10 7 AFUs of the at least one strain of P. hiranonis per kilogram body weight of the dog.

47. The method of any of claims 33-46, wherein the pharmaceutically acceptable carrier comprises a solid or a liquid.

48. The method of claim 47, wherein the pharmaceutically acceptable carrier comprises maltodextrin or microcrystalline cellulose.

49. The method of any of claims 33-48, wherein the probiotic composition is formulated for oral administration.

50. The method of any of claims 33-49, wherein the composition comprises microbes of P. hiranonis as deposited at BCCM under the accession number LMG P-33647 or LMG P-33648 and derivatives thereof.

51. The method of any of claims 33-49, wherein the composition comprises microbes of P. hiranonis as deposited at BCCM under the accession number LMG P-33640, LMGP-33642, or LMG P-33643 and derivatives thereof.

52. The method of treatment, as in any of claims 33-51, wherein the administration of the effective amount of the probiotic composition to the dog for at least 28 days consecutively increases relative abundance of the population of P. hiranonis in the gutAttorney Docket No. 117693.00024 of the subject dog upon treatment compared to dogs not administered the effective amount of the probiotic composition.

53. The method of any of claims 33-51, wherein the at least one strain of P. hiranonis continues to be retained in the gut of the dog at least 14 days after the probiotic was stopped.

54. A probiotic composition comprising:(a) purified and lyophilized P. hiranonis microbes comprising: microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33647 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33647; and / or microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33648 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33648; and / or microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33640 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33640; and / or microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33642 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33642; and / or microbes having at least 98% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33643 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33643; and(b) one or more pharmaceutically acceptable carriers suitable for dog administration; wherein the P. hiranonis microbes are in an amount effective to improve one or more traits in a dog administered the composition.Attorney Docket No. 117693.0002455. The probiotic composition of claim 54, wherein: the purified and lyophilized P. hiranonis microbes comprise: microbes having at least 98.4% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33647 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33647; and / or microbes having at least 98.4% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33648 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33648.

56. The probiotic composition of claim 55, wherein the microbes comprise nucleic acid sequences having at least 99.2% sequence identity to any of any of SEQ ID NOs: 1- 114; 115-215; 216-321; 322; and 323.

57. The probiotic composition of claim 54, wherein: the purified and lyophilized P. hiranonis microbes comprise: microbes having at least 98.4% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33640 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33640; and / or microbes having at least 98.4% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33642 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33642; and / or microbes having at least 98.4% average nucleotide identity (ANI) to microbes deposited with the BCCM under the accession number LMG P-33643 and / or microbes of a strain or isolate for which a representative sample was deposited with the BCCM under the accession number LMG P-33643;(b) one or more pharmaceutically acceptable carriers suitable for dog administration; wherein the P. hiranonis microbes are in an amount effective to improve one or more traits in a dog administered the composition.Attorney Docket No. 117693.0002458. The probiotic composition of claim 57, wherein the microbes comprise nucleic acid sequences having at least 99.2% sequence identity to any of SEQ ID NOs: 1-114; 115-215; 216-321; 322; and 323.

59. The probiotic composition of any of claims 54-58, wherein the one or more traits that are improved upon administration of the probiotic composition are selected from fecal quality and consistency, prevention of colonization of pathogenic microbes, and clearance of pathogenic microbes.

60. The probiotic composition of any of claims 54-59, wherein the composition comprises 10A3 CFUs / ml to 10A10 CFUs / ml of the P. hiranoms microbes.

61. The probiotic composition of any of claims 54-60, wherein the carrier is chosen from microcrystalline cellulose or maltodextrin.

62. The probiotic composition of any of claims 54-61 wherein the composition is formulated as a solid for oral administration by coating the composition partially or completely in an enteric coating that disintegrates only in the small intestine of a companion animal.

63. A composition comprising: at least one strain of a Peptacetobacter hiranoms species; and a pharmaceutically acceptable carrier, wherein the composition comprises microbes from one or more of the following P. hiranoms strains: microbes of the strain for which a representative sample was deposited with the Belgian Coordinated Collections of Microorganisms (BCCM) under the accession number LMG P-33640 or a taxonomic variant thereof having at least 98% average nucleotide identity (ANI) to LMG P-33640; microbes of the strain for which a representative sample was deposited with the BCCM under the accession number LMG P-33642 having at least 98% average nucleotide identity (ANI) to LMG P-33642;Attorney Docket No. 117693.00024 microbes of the strain for which a representative sample was deposited with the BCCM under the accession number LMG P-33643 having at least 98% average nucleotide identity (ANI) to LMG P-33643; microbes of the strain for which a representative sample was deposited with the BCCM under the accession number LMG P-33647 having at least 98% average nucleotide identity (ANI) to LMG P-33647; and / or microbes of the strain for which a representative sample was deposited with the BCCM under the accession number LMG P-33648 having at least 98% average nucleotide identity (ANI) to LMG P-33648.

64. The composition of claim 63, wherein the P. hiranonis microbe or microbes exhibit bile acid 7P dehydroxylation pathway activity and / or bile acid 7a dehydroxylation pathway activity.

65. The composition of claim 63 or 64, wherein the P. hiranonis microbes convert cholic acid to deoxycholic acid and / or convert chenodeoxy cholic acid to lithocholic acid.

66. The composition of any of claims 63-65 for use in the preparation of a veterinary medicant for treating a gastrointestinal condition in an animal.

67. A method of treating a gastrointestinal disorder in an animal, the method comprising administering to the animal the composition of any of claims 63-65.

68. A method of increasing bile acid metabolism in an animal, the method comprising administering to the animal the composition of any of claims 63-65 and 67.

69. The method of any of claims 67-68 wherein the animal is a dog.

70. A probiotic composition wherein the microbes comprise nucleic acid sequences having at least 99.2% sequence identity to any of SEQ ID NOs: 1-114.

71. A probiotic composition wherein the microbes comprise nucleic acid sequences having at least 99.2% sequence identity to any of SEQ ID NOs: 115-215.Attorney Docket No. 117693.00024H. A probiotic composition wherein the microbes comprise nucleic acid sequences having at least 99.2% sequence identity to any of SEQ ID NOs: 216-321.

73. A probiotic composition wherein the microbes comprise nucleic acid sequences having at least 99.2% sequence identity to any of SEQ ID NO: 322.

74. A probiotic composition wherein the microbes comprise nucleic acid sequences having at least 99.2% sequence identity to any of SEQ ID NO: 323.

75. A method of treating a gastrointestinal condition in an animal, the method comprising administering to the animal the microbial composition of any of claims 1-18. 54-65 and 70-74.

76. A method of increasing bile acid metabolism in an animal, the method comprising administering to the animal the composition of any of claims 1-18, 54-65 and 70-74.

77. A method of treating dysbiosis in an animal, the method comprising administering to the animal the composition of any of claims 1-18, 54-65 and 70-74.

78. The method of any of claims 75-77, wherein the animal is a dog.

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