Microbial CONSORTIA

Abstract

The present disclosure provides a microbial consortium comprising O. formigenes that can stably colonize the digestive tract of a subject, as well as methods of using and producing the same. The present disclosure relates to compositions and methods for reducing oxalate in a subject. In certain non-limiting embodiments, the present disclosure provides a composition comprising at least one oxalate metabolizing microbial strain. In certain embodiments, the at least one strain expresses an enzyme selected from formyl-CoA transferase, oxalate-formate exchanger, and oxalyl-CoA decarboxylase. In certain embodiments, the at least one oxalate metabolizing microbial strain is from the genus Oxalobacter.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 63 / 285,010, filed December 1, 2021, and U.S. Provisional Patent Application No. 63 / 305,476, filed February 8, 2022, the contents of each of which are incorporated by reference herein in their entirety and each of which priority is claimed.

[0002] Sequence Listing This application contains a Sequence Listing that has been submitted electronically in XML format, which is hereby incorporated by reference in its entirety. Said XML copy, created on November 30, 2022, is named 091592.0106.xml and is 393,216 bytes in size.

[0003] FIELD OF THEINVENTION The present disclosure relates generally to microbial consortia for administration to animals to degrade disease-related metabolic substrates. [Background technology]

[0004] background The gastrointestinal tract contains various biological niches along its longitudinal length, and these niches have different physical, chemical and nutritional compositions. As a result of these diverse conditions, specific microbial communities are established within specific biological niches. The microbial species that compose the specific microbial communities are highly responsive to their local environment and produce numerous bioactive molecules that aid in host survival, intermicrobial communication, nutrient metabolism, and incorporation or exclusion of competing microbial species. To further complicate matters, the microbial species and strains in the human gastrointestinal tract are quite diverse among individuals, which may be attributed to several factors, including genetics, diet, use of antibiotics and antifungals, surgical interventions (e.g., gastric bypass / intestinal resection), the presence of inflammatory bowel disease and / or irritable bowel syndrome, and other environmental influences. However, despite this interindividual diversity, the functional attributes of the various human gut microbiota are relatively consistent among healthy adults, including central metabolic pathways involved in carbohydrate metabolism, amino acid metabolism, fermentation and oxidative phosphorylation.

[0005] Modulation of microbial species in the digestive tract by using antibiotics, antifungals, and more recently fecal microbial transplantation ("FMT") has become a method of clinical investigation for the treatment and / or prevention of certain diseases and disorders.For example, Dodd et al. (Nature, 2007, 551: 648-652) propose FMT as a therapeutic method to modulate the level of aromatic amino acid metabolites in the serum of gnotobiotic mice, which affect intestinal permeability and systemic immunity.In a further example, administration of bacterial compositions has also been proposed as a method for treating Clostridium difficile infection, ulcerative colitis, cholestatic disease, and hyperoxaluria. There is a need for microbial compositions containing multiple microbial species with improved therapeutic efficacy and the ability to efficiently colonize, grow, and metabolize pathogenic substrates into non-pathogenic metabolites in various biological niches of the gastrointestinal tract of different individuals and in diverse gastrointestinal environments as a modality for treating various diseases and / or conditions. Furthermore, there is an unmet need for disease treatment using complex microbial communities that can colonize the human gastrointestinal tract and function there in a mutualistic manner for the degradation of disease-related metabolic substrates. [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] Dodd et al. (Nature, 2007, 551: 648-652) Summary of the Invention [Means for solving the problem]

[0007] Summary of the Invention The present disclosure relates to compositions and methods for reducing oxalate in a subject.In certain non-limiting embodiments, the present disclosure provides a composition comprising at least one oxalate metabolizing microbial strain.In certain embodiments, the at least one strain expresses an enzyme selected from formyl-CoA transferase, oxalate-formate exchanger, and oxalyl-CoA decarboxylase.In certain embodiments, the at least one oxalate metabolizing microbial strain is from the genus Oxalobacter.

[0008] In certain embodiments, the composition comprises at least three oxalate metabolizing microbial strains.In certain embodiments, the at least three oxalate metabolizing microbial strains are different strains of the same species.In certain embodiments, the at least three oxalate metabolizing microbial strains are different strains of different species.

[0009] In certain embodiments, the species is Oxalobacter formigenes (O. formigenes), and optionally the number of oxalate metabolizing microbial strains is three or more. In certain embodiments, a) at least one strain is a low pH tolerant strain; b) at least one strain is a high oxalate resistant strain; and / or c) At least one of the strains is a high growth rate strain.

[0010] In certain non-limiting embodiments, the present disclosure provides compositions comprising at least two Oxalobacter formigenes (O. formigenes) strains, each of the strains comprising one or more of the following features: a) a low pH tolerant strain; b) a high oxalate tolerant strain; and / or c) a high growth rate strain.

[0011] The present disclosure further provides a composition comprising at least three Oxalobacter formigenes (O. formigenes) strains, where a) at least one strain is a low pH tolerant strain; b) at least one strain is a high oxalate tolerant strain; and c) at least one strain is a high growth rate strain.

[0012] In certain embodiments, the low pH tolerant strain is capable of metabolizing oxalate at a pH between about 4 and about 6. In certain embodiments, the low pH tolerant strain is capable of metabolizing oxalate at a pH of about 5. In certain embodiments, the high oxalate tolerant strain is capable of metabolizing oxalate at a concentration between about 5 mM and about 30 mM. In certain embodiments, the high oxalate tolerant strain is capable of metabolizing oxalate at a concentration of about 15 mM.

[0013] In certain embodiments, each strain comprises a 16s RNA nucleotide sequence that is (a) at least about 80% identical to the nucleotide sequence set forth in SEQ ID NO:42, SEQ ID NO:79, or SEQ ID NO:146, (b) at least about 90% identical to the nucleotide sequence set forth in SEQ ID NO:42, SEQ ID NO:79, or SEQ ID NO:146, or (c) at least about 96% identical to the nucleotide sequence set forth in SEQ ID NO:42, SEQ ID NO:79, or SEQ ID NO:146. In certain embodiments, each strain comprises a 16s RNA nucleotide sequence that is at least about 97% identical or 98.5% identical to the nucleotide sequence set forth in SEQ ID NO:42, SEQ ID NO:79, or SEQ ID NO:146. In certain embodiments, each strain comprises a 16s RNA nucleotide sequence that is identical to the nucleotide sequence set forth in SEQ ID NO:42, SEQ ID NO:79, or SEQ ID NO:146.

[0014] In certain embodiments, the composition further comprises one or more microorganisms that metabolize formate. In certain embodiments, the composition further comprises one or more microorganisms that catalyze the fermentation of a polysaccharide. In certain embodiments, the composition further comprises one or more microorganisms that catalyze the fermentation of an amino acid. In certain embodiments, the composition further comprises a microorganism that catalyzes the synthesis of at least one molecule selected from the group consisting of methane, acetate, sulfide, propionate, and succinate. In certain embodiments, the composition further comprises a microorganism that catalyzes the degradation of a conjugated bile acid to produce a primary bile acid. In certain embodiments, the composition further comprises a microorganism that catalyzes the conversion of cholic acid (CA) to 7-oxocholic acid. In certain embodiments, the composition further comprises a microorganism that catalyzes the conversion of 7-oxocholic acid to 7-beta-cholic acid (7betaCA). In certain embodiments, the composition further comprises a microorganism that catalyzes the conversion of chenodeoxycholic acid (CDCA) to 7-oxo-chenodeoxycholic acid. In certain embodiments, the composition further comprises a microorganism that catalyzes the conversion of 7-oxochenodeoxycholic acid to ursodeoxycholic acid (UDCA).

[0015] In certain embodiments, the composition is selected from the group consisting of: a) Consortia I or a functional equivalent thereof; b) Consortia II or a functional equivalent thereof; c) Consortia III or a functional equivalent thereof; d) Consortia IV or a functional equivalent thereof; e) Consortia V or a functional equivalent thereof; f) Consortia VI or a functional equivalent thereof; g) Consortia VII or a functional equivalent thereof; h) Consortia VIII or a functional equivalent thereof; i) Consortia IX or a functional equivalent thereof; j) Consortia X or a functional equivalent thereof; k) Consortia XI or a functional equivalent thereof; l) Consortia XII or a functional equivalent thereof; m) Consortia XIII or a functional equivalent thereof; n) Consortia XIV or a functional equivalent thereof; o) Consortia XV or a functional equivalent thereof; p) Consortia XVI or a functional equivalent thereof; q) Consortia XVII or a functional equivalent thereof; r) Consortia XVIII or a functional equivalent thereof; or s) Consortia XIX or a functional equivalent thereof.

[0016] In certain embodiments, the composition comprises Clostridium citoniae, Bacteroides salyersiae, Blautia obeum, Parabacteroides merdae, Parabacteroides distasonis, Anaerostipes hadrus, Lachnospiraceae sp. FBI00033, Eubacterium eligens, Bifidobacterium dentium, Blautia wexlerae, Fusicatenibacter saccharivorans, Bacteroides nordii, Dorea formicigenerans, Dorea longicatena, Bacteroides stercorirosoris, Bifidobacterium longum, Bacteroides kribbi, Lachnospiraceae sp. FBI00071, Bacteroides thetaiotaomicron, Clostridium clostridioforme, Clostridium scindens, Roseburia hominis, Clostridium fessum, Coprococcus comes, Blautia faecis, Hungatella hathewayi, Bacteroides stercoris, Collinsella aerofaciens, Hungatella effluvii, Bifidobacterium adolescentis, Bifidobacterium catenulatum, Lactobacillus rogosae, Bacteroides faeces, Bacteroides finegoldii, Clostridiaceae sp.FBI00191, Ruminococcus faecis, Lachnoclostridium pacaense, Clostridium bolteae, Longicatena caecimuris, Eggerthella lenta, Blautia massiliensis, Bacteroides xylanisolvens, Bacteroides vulgatus, Megasphaera massiliensis, Butyricimonas faecihominis, Eisenbergiella tayi, Acidaminococcus intestini, Emergencia timonensis, Bifidobacterium pseudocatenulatum, Eubacterium hallii, Anaerofustis stercorihominis, Eubacterium ventriosum, Blautia hydrogenotrophica, Lachnospiraceae sp. FBI00290, or a functionally equivalent microbial consortium.

[0017] In certain embodiments, the composition is selected from the group consisting of FBI00001, FBI00002, FBI00010, FBI00013, FBI00029, FBI00032, FBI00033, FBI00034, FBI00043, FBI00044, FBI00048, FBI00050, FBI00051, FBI00057, FBI00059, FBI00060, FBI00070, FBI00071, FBI00076, FBI00079, FBI00087, FBI00093, FBI00102, FBI00109, FBI00117, FBI00120, FBI00125, FBI00127, FBI00128, FBI00145, FBI00162, FBI00174, FBI00184, FBI00190, FBI00191, FBI00194, FBI00198, FBI00199, FBI00200, FBI00201, FBI00205, FBI00206, FBI00211, FBI00220, FBI00221, FBI00236, FBI00245, FBI00248, FBI00251, FBI00254, FBI00267, FBI00278, FBI00288, FBI00290, or a functional equivalent thereof.

[0018] In certain embodiments, each strain comprises (a) the sequences of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:83, SEQ ID NO:89, SEQ ID NO:94, SEQ ID NO:100, (b) at least about 80% identical to the nucleotide sequence set forth in SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, Column number 25, SEQ ID NO:26, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:83, SEQ ID NO:89, SEQ ID NO:94, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO: or (c) is at least about 90% identical to the nucleotide sequence set forth in SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:45, SEQ ID NO:46,The nucleotide sequence of the 16s RNA is at least about 96% identical to the nucleotide sequence set forth in SEQ ID NO:48, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:83, SEQ ID NO:89, SEQ ID NO:94, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:136, SEQ ID NO:143, SEQ ID NO:145, or SEQ ID NO:147.

[0019] In certain embodiments, each strain is selected from SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ 9, SEQ ID NO:94, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:136, SEQ ID NO:143, SEQ ID NO:145, or SEQ ID NO:147.

[0020] In certain embodiments, each strain is selected from the group consisting of the following SEQ ID NOs: SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77 , SEQ ID NO:83, SEQ ID NO:89, SEQ ID NO:94, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:136, SEQ ID NO:143, SEQ ID NO:145, or SEQ ID NO:147.

[0021] In certain embodiments, the composition comprises: Acutalibacter timonensis, Alistipes onderdonkii, Bacteroides uniformis, Eubacterium rectale, Alistipes timonensis, Bacteroides kribbi, Coprococcus eutactus, Bilophila wadsworthia, Bacteroides caccae, Alistipes shahii, Parasutterella excrementihominis, Paraprevotella clara, Sutterella wadsworthensis, Sutterella massiliensis, Porphyromonas asaccharolytica, Ruminococcus bromii, Monoglobus pectinolyticus, Ruminococcaceae sp. FBI00097, Gordonibacter pamelaeae, Bacteroides uniformis, Gordonibacter pamelaeae, Bacteroides fragilis, Phascolarctobacterium faecium, Monoglobus pectinolyticus, Clostridium aldenense, Ruthenibacterium lactatiformans, Bacteroides ovatus, Bifidobacterium bifidum, Anaerotruncus massiliensis, Clostridium aldenense, Sutterella wadsworthensis, Catabacter hongkongensis, Alistipes senegalensis、Ruminococcaceae sp.FBI00233, Alistipes shahii, Dielma fastidiosa, Eubacterium siraeum, Faecalibacterium prausnitzii, Turicibacter sanguinis, Eubacterium rectale, Bacteroides caccae, Methanobrevibacter smithii, Barnesiella intestinihominis, Alistipes onderdonkii, Methanobrevibacter smithii, or a functional equivalent thereof.

[0022] In certain embodiments, the composition is selected from the group consisting of FBI00004, FBI00012, FBI00015, FBI00018, FBI00019, FBI00021, FBI00038, FBI00040, FBI00046, FBI00061, FBI00066, FBI00075, FBI00077, FBI00080, FBI00081, FBI00085, FBI00092, FBI00097, FBI00099, FBI00112, FBI00132, FBI00137, FBI00140, FBI00142, FBI00144, FBI00146, FBI00148 ... 140, FBI00149, FBI00151, FBI00176, FBI00189, FBI00197, FBI00208, FBI00212, FBI00224, FBI00226, FBI00229, FBI00233, FBI00235, FBI00237, FBI00243, FBI00244, FBI00258, FBI00260, FBI00263, FBI00270, FBI00273, FBI00277, FBI00292, or a functional equivalent thereof.

[0023] In certain embodiments, each strain comprises (a) the sequences of SEQ ID NO:3, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:27, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:66, SEQ ID NO:78, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:96, SEQ ID NO:101, SEQ ID NO:105, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO: (b) at least about 80% identical to the nucleotide sequence set forth in SEQ ID NO:3, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:27, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:54, SEQ ID NO:56, or (c) is at least about 90% identical to the nucleotide sequence set forth in SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:66, SEQ ID NO:78, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:96, SEQ ID NO:101, SEQ ID NO:105, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, or SEQ ID NO:148; or Column number 3, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:27, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:66, SEQ ID NO:78, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:96, SEQ ID NO:101, SEQ ID NO:105, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:122,The nucleotide sequence of the 16s RNA is at least about 96% identical to the nucleotide sequence set forth in SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, or SEQ ID NO:148.

[0024] In certain embodiments, each strain comprises a 16s RNA nucleotide sequence that is at least about 97% identical or 98.5% identical to the nucleotide sequence set forth in SEQ ID NO:3, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:27, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:66, SEQ ID NO:78, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:96, SEQ ID NO:101, SEQ ID NO:105, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, or SEQ ID NO:148.

[0025] In certain embodiments, each strain comprises a 16s RNA nucleotide sequence identical to the nucleotide sequence set forth in SEQ ID NO:3, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:27, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:66, SEQ ID NO:78, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:96, SEQ ID NO:101, SEQ ID NO:105, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, or SEQ ID NO:148.

[0026] In certain embodiments, the composition comprises Bifidobacterium adolescentis, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bacteroides thetaiotaomicron, Coprococcus comes, Fusicatenibacter saccharivorans, Eggerthella lenta, Eubacterium eligens, Bacteroides xylanisolvens, Lactobacillus rogosae, Clostridium citroniae, Collinsella aerofaciens, Blautia obeum, Eggerthella lenta, Blautia wexlerae, Lachnoclostridium pacaense, Bacteroides vulgatus, Parabacteroides merdae, Dorea formicigenerans, Ruminococcus faecis, Roseburia hominis, Anaerostipes hadrus, Bifidobacterium adolescentis, Bifidobacterium and a fourth composition comprising Bacteroides pseudocatenulatum, Clostridium bolteae, Eisenbergiella tayi, Dorea longicatena, Eggerthella lenta, Bacteroides stercoris, Hungatella hathewayi, Bacteroides xylanisolvens, or functional equivalents thereof.

[0027] In certain embodiments, the composition is selected from the group consisting of FBI00009, FBI00011, FBI00016, FBI00020, FBI00025, FBI00027, FBI00030, FBI00047, FBI00052, FBI00053, FBI00056, FBI00062, FBI00078, FBI00096, FBI00104, FBI00058, FBI00060, FBI00079, FBI00080, FBI00092, FBI00094, FBI000106, FBI000110, FBI000120, FBI000140, FBI000160, FBI000181, FBI000182, FBI000161, FBI000183, FBI000184, FBI000185, FBI000186, FBI000187, FBI000188, FBI000189, FBI000200, FBI00020102, FBI000203, FBI000204, FBI00022, FBI00024, FBI00026, FBI000285, FBI000286, FBI000287, FBI000289, FBI00030, FBI00040, FBI00041, FBI00042, FBI00043, FBI00044, FBI00045, FBI00046, FBI00047, FBI00052, FBI00053, FBI00056, F FBI00135, FBI00147, FBI00159, FBI00167, FBI00170, FBI00232, FBI00255, FBI00271, or functional equivalents thereof.

[0028] In certain embodiments, each strain is (a) at least about 80% identical to the nucleotide sequence set forth in SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:10, SEQ ID NO:13, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:28, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:40, SEQ ID NO:50, SEQ ID NO:58, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:88, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:120, SEQ ID NO:132, or SEQ ID NO:139; (b) at least about 80% identical to the nucleotide sequence set forth in SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:10, SEQ ID NO:13, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:28, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:40, SEQ ID NO:50, SEQ ID NO:58, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, or (c) a 16s RNA nucleotide sequence that is at least about 90% identical to the nucleotide sequence set forth in SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:88, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:120, SEQ ID NO:132, or SEQ ID NO:139; or (b) a 16s RNA nucleotide sequence that is at least about 96% identical to the nucleotide sequence set forth in SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:10, SEQ ID NO:13, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:28, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:40, SEQ ID NO:50, SEQ ID NO:58, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:88, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:120, SEQ ID NO:132, or SEQ ID NO:139.

[0029] In certain embodiments, each strain comprises a 16s RNA nucleotide sequence that is at least about 97% identical or 98.5% identical to the nucleotide sequence set forth in SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:10, SEQ ID NO:13, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:28, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:40, SEQ ID NO:50, SEQ ID NO:58, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:88, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:120, SEQ ID NO:132, or SEQ ID NO:139. In certain embodiments, each strain comprises a 16s RNA nucleotide sequence identical to the nucleotide sequence set forth in SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:10, SEQ ID NO:13, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:28, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:40, SEQ ID NO:50, SEQ ID NO:58, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:88, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:120, SEQ ID NO:132, or SEQ ID NO:139.

[0030] In certain embodiments, the composition further comprises a fifth composition comprising Alistipes putredinis, Dialister succinatiphilus, Akkermansia muciniphila, Ruminococcus bromii, Dialister invisus, Bacteroides massiliensis, Bilophila wadsworthia, Holdemanella biformis, Parasutterella excrementihominis, Alistipes sp. FBI00180, Bacteroides coprocola, Alistipes sp. FBI00238, Alistipes putredinis, Eubacterium xylanophilum, Senegalimassilia anaerobia, or a functional equivalent thereof.

[0031] In certain embodiments, the composition further comprises FBI00022, FBI00049, FBI00068, FBI00069, FBI00152, FBI00165, FBI00171, FBI00175, FBI00177, FBI00180, FBI00182, FBI00238, FBI00269, FBI00274, FBI00281, or a functional equivalent thereof.

[0032] In certain embodiments, each strain comprises a 16s sequence that is (a) at least about 80% identical to the nucleotide sequence set forth in SEQ ID NO:15, SEQ ID NO:30, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:87, SEQ ID NO:90, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:125, SEQ ID NO:137, SEQ ID NO:141, or SEQ ID NO:144; (b) at least about 90% identical to the nucleotide sequence set forth in SEQ ID NO:15, SEQ ID NO:30, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:87, SEQ ID NO:90, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:125, SEQ ID NO:137, SEQ ID NO:141, or SEQ ID NO:144; or (c) at least about 96% identical to the nucleotide sequence set forth in SEQ ID NO:15, SEQ ID NO:30, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:87, SEQ ID NO:90, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:125, SEQ ID NO:137, SEQ ID NO:141, or SEQ ID NO:144. Contains an RNA nucleotide sequence.

[0033] In certain embodiments, each strain comprises a 16s RNA nucleotide sequence that is at least about 97% identical or 98.5% identical to the nucleotide sequence set forth in SEQ ID NO:15, SEQ ID NO:30, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:87, SEQ ID NO:90, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:125, SEQ ID NO:137, SEQ ID NO:141, or SEQ ID NO:144.

[0034] In certain embodiments, each strain comprises a 16s RNA nucleotide sequence identical to the nucleotide sequence set forth in SEQ ID NO:15, SEQ ID NO:30, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:87, SEQ ID NO:90, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:125, SEQ ID NO:137, SEQ ID NO:141, or SEQ ID NO:144.

[0035] Further, the present disclosure provides a microbial consortium comprising a microbial strain set forth in Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, Table 10, Table 11, Table 12, Table 13, Table 14, Table 15, Table 16, Table 17, Table 18, Table 19, or a functional equivalent thereof.

[0036] The present disclosure also provides a microbial consortium comprising a microbial strain set forth in Table 22, or a functional equivalent thereof.

[0037] In certain embodiments, each strain comprises a 16s RNA nucleotide sequence that is (a) at least about 80% identical to a nucleotide sequence set forth in SEQ ID NOs:1-148, (b) at least about 90% identical to a nucleotide sequence set forth in SEQ ID NOs:1-148, or (c) at least about 96% identical to a nucleotide sequence set forth in SEQ ID NOs:1-148. In certain embodiments, each strain comprises a 16s RNA nucleotide sequence that is at least about 97% identical to a nucleotide sequence set forth in SEQ ID NOs:1-148, or 98.5% to that nucleotide sequence. In certain embodiments, each strain comprises a 16s RNA nucleotide sequence that is identical to a nucleotide sequence set forth in SEQ ID NOs:1-148.

[0038] The present disclosure further provides compositions comprising the microbial consortia disclosed herein.

[0039] In certain embodiments, the compositions disclosed herein are pharmaceutical compositions.

[0040] In certain embodiments, the composition comprises about 5×10 10 ~Approx. 5×10 11In certain embodiments, the composition comprises about 5×10 viable cells. 9 ~Approx. 5×10 10 In certain embodiments, the composition comprises about 5×10 viable cells. 11 ~Approx. 5×10 12 In certain embodiments, the composition comprises up to about 5×10 viable cells. 12 Contains living cells.

[0041] In certain embodiments, the composition comprises about 10% to about 50% of the oxalate metabolizing microbial strain. In certain embodiments, the composition comprises about 10% to about 50% of the O. formigenes strain on a viable cell count basis. In certain embodiments, the composition comprises about 20% of the O. formigenes strain on a viable cell count basis. In certain embodiments, the composition comprises about 30% of the O. formigenes strain on a viable cell count basis. In certain embodiments, the composition comprises about 40% of the O. formigenes strain on a viable cell count basis.

[0042] The present disclosure further provides a method of producing the compositions or microbial consortia disclosed herein. In certain embodiments, the method comprises: a) Clostridium citroniae, Bacteroides salyersiae, Blautia obeum, Parabacteroides merdae, Parabacteroides distasonis, Anaerostipes hadrus, Lachnospiraceae sp.FBI00033, Eubacterium eligens, Bifidobacterium dentium, Blautia wexlerae, Fusicatenibacter saccharivorans, Bacteroides nordii, Dorea formicigenerans, Dorea longicatena, Bacteroides stercorirosoris, Bifidobacterium longum, Bacteroides kribbi, Lachnospiraceae sp.FBI00071, Bacteroides thetaiotaomicron, Clostridium clostridioforme, Clostridium scindens, Roseburia hominis, Clostridium fessum, Coprococcus comes, Blautia faecis, Hungatella hathewayi, Bacteroides stercoris, Collinsella aerofaciens, Hungatella effluvii, Bifidobacterium adolescentis, Bifidobacterium catenulatum, Lactobacillus rogosae, Bacteroides faecis, Bacteroides finegoldii、Clostridiaceae sp.A first composition comprising FBI00191, Ruminococcus faecis, Lachnoclostridium pacaense, Clostridium bolteae, Longicatena caecimuris, Eggerthella lenta, Blautia massiliensis, Bacteroides xylanisolvens, Bacteroides vulgatus, Megasphaera massiliensis, Butyricimonas faecihominis, Eisenbergiella tayi, Acidaminococcus intestini, Emergencia timonensis, Bifidobacterium pseudocatenulatum, Eubacterium hallii, Anaerofustis stercorihominis, Eubacterium ventriosum, Blautia hydrogenotrophica, and Lachnospiraceae sp. FBI00290, or a functional equivalent thereof;. b) Acutalibacter timonensis, Alistipes onderdonkii, Bacteroides uniformis, Eubacterium rectale, Alistipes timonensis, Bacteroides kribbi, Coprococcus eutactus, Bilophila wadsworthia, Bacteroides caccae, Alistipes shahii, Parasutterella excrementihominis, Paraprevotella clara, Sutterella wadsworthensis, Sutterella massiliensis, Porphyromonas asaccharolytica, Ruminococcus bromii, Monoglobus pectinolyticus, Ruminococcaceae sp.FBI00097, Gordonibacter pamelaeae, Bacteroides uniformis, Gordonibacter pamelaeae, Bacteroides fragilis, Phascolarctobacterium faecium, Monoglobus pectinolyticus, Clostridium aldenense, Ruthenibacterium lactatiformans, Bacteroides ovatus, Bifidobacterium bifidum, Anaerotruncus massiliensis, Clostridium aldenense, Sutterella wadsworthensis, Catabacter hongkongensis, Alistipes senegalensis、Ruminococcaceae sp.a second composition comprising FBI00233, Alistipes shahii, Dielma fastidiosa, Eubacterium siraeum, Faecalibacterium prausnitzii, Turicibacter sanguinis, Eubacterium rectale, Bacteroides caccae, Methanobrevibacter smithii, Barnesiella intestinihominis, Alistipes onderdonkii, and Methanobrevibacter smithii, or functional equivalents thereof; c) a third composition comprising Bifidobacterium adolescentis, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bacteroides thetaiotaomicron, Coprococcus comes, Fusicatenibacter saccharivorans, Eggerthella lenta, Eubacterium eligens, Bacteroides xylanisolvens, Lactobacillus rogosae, Clostridium citoniae, Collinsella aerofaciens, Blautia obeum, Eggerthella lenta, Blautia wexlerae, Lachnoclostridium pacaense, Bacteroides vulgatus, Parabacteroides merdae, Dorea formicigenerans, Ruminococcus faecis, Roseburia hominis, Anaerostipes hadrus, Bifidobacterium adolescentis, Bifidobacterium pseudocatenulatum, Clostridium bolteae, Eisenbergiella tayi, Dorea longicatena, Eggerthella lenta, Bacteroides stercoris, Hungatella hathawayi, and Bacteroides xylanisolvens, or functional equivalents thereof; d) a fourth composition comprising Alistipes putredinis, Dialister succinatiphilus, Akkermansia muciniphila, Ruminococcus bromii, Dialister invisus, Bacteroides massiliensis, Bilophila wadsworthia, Holdemanella biformis, Parasutterella excrementihominis, Alistipes sp. FBI00180, Bacteroides coprocola, Alistipes sp. FBI00238, Alistipes putredinis, Eubacterium xylanophilum, and Senegalimassilia anaerobia, or a functional equivalent thereof; e) a fifth composition comprising the first O. formigenes strain; f) a sixth composition comprising a second O. formigenes strain; and / or g) A seventh composition comprising a third O. formigenes strain. and blending.

[0043] In certain embodiments, the method comprises: a) FBI00001, FBI00002, FBI00010, FBI00013, FBI00029, FBI00032, FBI00033, FBI00034, FBI00043, FBI00044, FBI00048, FBI00050, FBI00051, FBI00057, FBI00059, FBI00060, FBI00070, FBI00071, FBI00076, FBI00079, FBI00087, FBI00093, FBI00102, FBI00109, FBI00117, FBI00120, FBI00125, FBI00127, FB a first composition comprising FBI00128, FBI00145, FBI00162, FBI00174, FBI00184, FBI00190, FBI00191, FBI00194, FBI00198, FBI00199, FBI00200, FBI00201, FBI00205, FBI00206, FBI00211, FBI00220, FBI00221, FBI00236, FBI00245, FBI00248, FBI00251, FBI00254, FBI00267, FBI00278, FBI00288, and FBI00290, or a functional equivalent thereof; b) FBI00004, FBI00012, FBI00015, FBI00018, FBI00019, FBI00021, FBI00038, FBI00040, FBI00046, FBI00061, FBI00066, FBI0007 5, FBI00077, FBI00080, FBI00081, FBI00085, FBI00092, FBI00097, FBI00099, FBI00112, FBI00132, FBI00137, FBI00140, FBI0014 9, FBI00151, FBI00176, FBI00189, FBI00197, FBI00208, FBI00212, FBI00224, FBI00226, FBI00229, FBI00233, FBI00235, FBI00237, FBI00243, FBI00244, FBI00258, FBI00260, FBI00263, FBI00270, FBI00273, FBI00277, and FBI00292, or a functional equivalent thereof; c) FBI00009, FBI00011, FBI00016, FBI00020, FBI00025, FBI00027, FBI00030, FBI00047, FB I00052, FBI00053, FBI00056, FBI00062, FBI00078, FBI00096, FBI00104, FBI00110, FBI0011 1, FBI00113, FBI00115, FBI00116, FBI00123, FBI00124, FBI00126, FBI00135, FBI00147, FBI00159, FBI00167, FBI00170, FBI00232, FBI00255, and FBI00271, or functional equivalents thereof; d) a fourth composition comprising FBI00022, FBI00049, FBI00068, FBI00069, FBI00152, FBI00165, FBI00171, FBI00175, FBI00177, FBI00180, FBI00182, FBI00238, FBI00269, FBI00274, and FBI00281, or a functional equivalent thereof; e) a fifth composition comprising FBI00067 or a functional equivalent thereof; f) a sixth composition comprising FBI00133 or a functional equivalent thereof; and / or g) A seventh composition comprising FBI00289 or a functional equivalent thereof. and blending.

[0044] In certain embodiments, each strain comprises a 16s RNA nucleotide sequence that is (a) at least about 80% identical to a nucleotide sequence set forth in SEQ ID NOs:1-148, (b) at least about 90% identical to a nucleotide sequence set forth in SEQ ID NOs:1-148, or (c) at least about 96% identical to a nucleotide sequence set forth in SEQ ID NOs:1-148. In certain embodiments, each strain comprises a 16s RNA nucleotide sequence that is at least about 97% identical or 98.5% identical to a nucleotide sequence set forth in SEQ ID NOs:1-148. In certain embodiments, each strain comprises a 16s RNA nucleotide sequence identical to a nucleotide sequence set forth in SEQ ID NOs:1-148.

[0045] In certain embodiments, the fourth composition is obtained by growing the microorganism in the presence of threonine. In certain embodiments, each composition comprises a lyoprotectant. In certain embodiments, each composition comprises maltodextrin, inulin, or a combination thereof. In certain embodiments, the maltodextrin is at a concentration of about 8%. In certain embodiments, the inulin is at a concentration of about 0.5%. In certain embodiments, each composition is lyophilized separately.

[0046] In certain embodiments, the functional equivalents are based on the features in Table 24. In certain embodiments, the functional equivalents are based on the features in Table 34. In certain embodiments, the functional equivalents are based on the features in Table 35. In certain embodiments, the functional equivalents are based on the features in Table 36. In certain embodiments, the functional equivalents are based on the features in Tables 34-36.

[0047] In certain embodiments, the method comprises obtaining and blending microorganisms that contain genes that regulate oxalate degradation, oxalate resistance, formate metabolism, macronutrient metabolism, microbial metabolite production, syntrophic activity, and / or mucin degradation. In certain embodiments, the method comprises obtaining and blending microorganisms that are known to prevent disease and / or are commonly found in the healthy human gut. In certain embodiments, the method comprises obtaining and blending microorganisms that utilize a carbon source listed in Table 35. In certain embodiments, each strain can utilize a subset of the carbon sources listed in Table 35 as needed.

[0048] In certain embodiments, each composition is prepared using inoculation density adjustments. In certain embodiments, each composition is cultured or has been cultured in the presence of a gas overlay. In certain embodiments, each composition is cultured or has been cultured in the absence of gas sparging.

[0049] The present disclosure also provides compositions prepared by the methods disclosed herein.

[0050] Additionally, the present disclosure provides methods of treating hyperoxaluria in a subject in need thereof, reducing the risk of developing hyperoxaluria in a subject in need thereof, and / or reducing urinary oxalate in a subject in need thereof. In certain embodiments, the methods comprise administering an effective amount of the composition or microbial consortium disclosed herein.

[0051] In certain embodiments, the hyperoxaluria is primary hyperoxaluria, secondary hyperoxaluria, or enteric hyperoxaluria. In certain embodiments, the secondary hyperoxaluria is associated with bowel resection surgery. In certain embodiments, the hyperoxaluria is enteric hyperoxaluria.

[0052] In certain embodiments, the method further comprises administering at least one antibacterial agent, antiviral agent, antifungal agent, anti-inflammatory agent, immunosuppressant, prebiotic, or a combination thereof. In certain embodiments, the method further comprises administering NOV-001, SYNB8802, OX-1, lumasiran, nedosiran, BBP-711, CNK-336, PBGENE-PH1, or a combination thereof. In certain embodiments, the method further comprises administering a low oxalate diet, a high hydration diet, a calcium supplement, or a combination thereof. In certain embodiments, the composition or microbial consortium is administered orally.

[0053] In certain embodiments, the method includes administering a first dose of a composition or microbial consortium disclosed herein.

[0054] In certain embodiments, the method further comprises administering an antibiotic treatment. In certain embodiments, the antibiotic treatment is administered for about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, or about 7 days. In certain embodiments, the antibiotic is metronidazole, clarithromycin, or a combination thereof. In certain embodiments, the antibiotic treatment is completed one day before administering the first dose. In certain embodiments, the antibiotic treatment is completed two days before administering the first dose.

[0055] In certain embodiments, the method further comprises administering a treatment that is a bowel preparation treatment. In certain embodiments, the treatment that is a bowel preparation treatment is administered to the subject after the antibiotic treatment. In certain embodiments, the treatment that is a bowel preparation treatment is administered before the first dose.

[0056] In certain embodiments, the first dose comprises an effective amount of the composition or microbial consortium. In certain embodiments, the first dose comprises about 10 12 In certain embodiments, the first dose is administered for about 1 day. In certain embodiments, the first dose is administered for about 2 days.

[0057] In certain embodiments, the method further comprises administering a second dose of the composition or microbial consortium. In certain embodiments, the second dose comprises an effective amount of the composition or microbial consortium. In certain embodiments, the second dose comprises about 10 11 In certain embodiments, the second dose is administered for up to about 8 days. In certain embodiments, the second dose is administered for up to about 10 days.

[0058] In certain embodiments, the first dose is administered orally. In certain embodiments, the second dose is administered orally.

[0059] The present disclosure also provides a kit comprising the composition or microbial consortium disclosed herein. In certain embodiments, the kit comprises a container comprising a desiccant. In certain embodiments, the container comprises anaerobic conditions. In certain embodiments, the container is a blister. In certain embodiments, the kit further comprises written instructions for administering the composition or microbial consortium.

[0060] The present disclosure also provides a method of culturing a microbial strain from the genus Akkermansia, comprising contacting the strain with N-acetylgalactosamine (GalNAc). In certain embodiments, the strain is Akkermansia muciniphilia.

[0061] The present disclosure also provides a microbial consortium comprising the functional properties set forth in Table 23, Table 24, Table 34, Table 35, Table 36. Finally, the present disclosure provides a microbial consortium comprising FB-001 or a functional equivalent thereof. [Brief description of the drawings]

[0062] [Figure 1A] FIG. 1A shows the reduction of urinary oxalate in mice fed a refined, high-sugar diet and force-fed Consortia as described herein. FIG. 1B shows the reduction of urinary oxalate in mice fed a complex, grain-free diet and force-fed Consortia as described herein. Taken together, FIGS. 1A and 1B show that the effectiveness of reducing urinary oxalate using Consortia as described herein is independent of diet. FIG. 1C shows that the gut microbiota present in the animals prior to treatment with Consortia as described herein does not affect the ability of Consortia to reduce urinary oxalate levels. [Figure 1B] Same as above. [Figure 1C] Same as above.

[0063] [Figure 2A]FIG. 2A shows an exemplary co-culture experiment, and FIG. 2B shows an exemplary co-culture experiment modified to result in 100% strain detection after co-culture. [Figure 2B] Same as above.

[0064] [Figure 3A-3B] FIG. 3A shows the design of the DS bucket for Consortia, and FIG. 3B shows the yield of strains after co-cultivation depending on the inoculation seed.

[0065] [Figure 4A] 4A and 4B show examples of different lyophilization excipients. [Figure 4B] Same as above.

[0066] [Figure 5A] 5A and 5B show examples of different lyophilization excipients and reducing agents. [Figure 5B] Same as above.

[0067] [Figure 6A] 6A and 6B show examples of different lyophilized excipients. [Figure 6B] Same as above. [Figure 7A] Figure 7A is a Venn diagram of overlapping microorganisms for five representative consortia designed and disclosed herein, and Figure 7B shows the breakdown of microbial types in each of the five representative consortia. [Figure 7B] Same as above.

[0068] [Figure 8A-8B] Figure 8A shows a graph plotting the induction of EH in germ-free mice using different diets (control and oxalate diets as described in Example 4), and Figure 8B shows a graph showing the relative abundance of O. formigenes and oxalate degradation.

[0069] [Figure 9]FIG. 9 shows the oxalate and Ox:Cr ratios in germ-free and "humanized" mice fed an oxalate diet.

[0070] [Figure 10A-10D] Figure 10A shows the relative abundance of O. formigenes following administration of community I (prevalence-based community), community II (two-donor community), community III (metabolism A community), community 4 (metabolism B community), or community 5 (diversity community). Figure 10B shows bacterial species richness in mice fed the Ox36 diet followed by administration of one of five representative consortia. Figure 10C shows bacterial species richness in mice fed the 5021+0.875% Ox diet followed by administration of one of five representative consortia. Figure 10D shows bacterial species richness in humanized mice administered one of five representative consortia.

[0071] [Figure 11A] 11A and 11B show a schematic of the experimental design of the study described in Example 5. [Figure 11B] Same as above.

[0072] [Figure 12] FIG. 12 shows that YCFAC+GalNAc is unable to support the growth of Akkermansia.

[0073] [Figure 13] FIG. 13 shows that threonine supports Akkermansia growth in the absence of GalNAc.

[0074] [Figure 14] FIG. 14 shows a schematic diagram of the co-culture method of manufacture.

[0075] [Figure 15] FIG. 15 shows an overview of the strain isolation and purification process, RCB bank construction, and RCB identity / purity testing.

[0076] [Figure 16] FIG. 16 shows a method for the generation of a Master Cell Bank (MCB).

[0077] [Figure 17] FIG. 17 shows a phylogenetic tree illustrating the taxonomic organization of the FB-001 Consortium.

[0078] [Figure 18A] 18A-18C show a table summarizing the strains and species of the microbial consortia disclosed herein. [Figure 18B] Same as above. [Figure 18C] Same as above.

[0079] [Figure 19A-19B] Figure 19A shows the effect of FB-001 in reducing intestinal permeability, and Figure 19B shows the ability of FB-001 to produce short chain fatty acids (SCFAs) at levels comparable to normal, healthy intestines. The SCFA butyrate is important because it supports gut epithelial cell health, energy metabolism, and cell signaling, improving barrier function.

[0080] [Figure 20A] Figures 20A-20D show that FB-001 reduces urinary oxalate (UrOx) by 35-68% in vivo across different diets (i.e., the ability of FB-001 and DS1-DS4 to reduce urinary oxalate is independent of diet and pre-existing microbiota). Figure 20A shows a depiction of the study design. Figure 20B shows the oxalate:creatinine ratios of mice fed a complex, grain-based diet. Figure 20C shows the oxalate:creatinine ratios of mice fed a refined, high sugar diet. Figure 20D shows the oxalate:creatinine ratios of humanized mice. [Fig. 20B-D] Same as above.

[0081] [Figure 21]Figure 21 shows a comparison made by mathematical modeling of the oxalate degradation rate (per cell) of FB-001 compared to Novome's WW554 and WW626 hyperoxaluria drugs and Synlogic's 8802 drug. The data shows that FB-001 can achieve oxalate consumption at a significantly higher rate than the other drugs, suggesting that FB-001 may be more effective for treating hyperoxaluria in subjects in need thereof.

[0082] [Figure 22] Figure 22 shows the manufacturing process used for O. formigenes in the production of Consortia described herein. Additionally, DS5-DS7 of FB-001 (i.e., the three O. formigenes drug substances) used this manufacturing process for GMP and non-GMP manufacturing.

[0083] [Figure 23] Figure 23 shows the manufacturing process used for DS1 in the production of Consortia described herein. Additionally, DS1 of FB-001 used this manufacturing process for GMP and non-GMP manufacturing.

[0084] [Figure 24] Figure 24 shows the manufacturing process used for DS2 in the production of Consortia described herein. Additionally, DS2 of FB-001 used this manufacturing process for GMP and non-GMP manufacturing.

[0085] [Diagram 25] Figure 25 shows the manufacturing process used for DS3 in the Consortia production described herein. Additionally, DS3 of FB-001 used this manufacturing process for GMP and non-GMP manufacturing.

[0086] [Figure 26]Figure 26 shows the manufacturing process used for DS4 in the production of Consortia described herein. Additionally, DS4 of FB-001 used this manufacturing process for GMP and non-GMP manufacturing. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0087] Detailed Description The present disclosure relates to compositions and methods for reducing oxalate in a subject. For clarity of explanation, and not by way of limitation, this section is divided into the following subsections: (a) Definition; (b) biological niche; (c) physical division; (d) metabolic compartments; (e) Consortia; (f) active microorganisms; (g) oxalate-metabolizing active microorganisms; (h) microbial support community; (j)Consortia design; (k) Preparation method; (i) a pharmaceutical composition; (l) Functionally equivalent and identical pharmaceutical products; (m) Therapeutic applications; (n) methods of treating hyperoxaluria; (o) dosage; (p) combination therapy; (q) kits; and (r) Exemplary embodiments. definition

[0088] Unless otherwise defined, all technical and scientific terms used herein have the meanings commonly understood by those skilled in the art.The following references provide those skilled in the art with general definitions for many of the terms used in relation to the subject matter of this disclosure: Singleton et al., Dictionary of Microbiology and Molecular Biology (2nd ed. 1994);The Cambridge Dictionary of Science and Technology (Walker ed., 1988);The Glossary of Genetics, 5th Ed., R. Rieger et al. (eds.), Springer Verlag (1991);And Hale & Marham, The Harper Collins Dictionary of Biology (1991).As used herein, the following terms have the meanings ascribed to them below, unless otherwise specified.

[0089] It will be understood that the aspects and embodiments of the present disclosure described herein include the aspects and embodiments "comprising," "consisting of," and "consisting essentially of."

[0090] The terms "comprises" and "comprising" are intended to have the broad meaning ascribed to them in U.S. patent law and can mean "includes," "including," etc.

[0091] To facilitate the understanding of this disclosure, several terms and phrases are defined below.

[0092] The terms "a" and "an" as used herein mean "one or more" and include plural terms, unless the context indicates otherwise.

[0093] As used herein, the term "active microorganism" refers to a microorganism that expresses one or more metabolic enzymes in sufficient amounts to metabolize a substrate that causes or contributes to disease in an animal.

[0094] As used herein, the term "biomass" refers to the total mass of one or more than one microorganism or consortium in a given area or volume.

[0095] As used herein, the terms "microbial consortia" and "microbial consortium" are used interchangeably and refer to a mixture of two or more isolated microbial strains grown in culture, where one microbial strain in the mixture has a beneficial or desired effect on another microbial strain in the mixture.

[0096] As used herein, the term "Consortia" is used as a capitalized term to refer to one or more of the microbial consortia described herein.

[0097] As used herein, the term "engraftment of the digestive tract" or "engrafting" or "engraftment" refers to the establishment of one or more microorganisms or a microbial consortium in one or more niches of the digestive tract that are absent in the one or more microorganisms or microbial consortium prior to administration of the one or more microorganisms or microbial consortium. Engraftment of the digestive tract can be temporary or persistent.

[0098] As used herein, the term "effective amount" refers to an amount sufficient to achieve beneficial or desired results.In certain embodiments, the effective amount is the improvement of the engraftment of one or more of the multiple active microorganisms in the digestive tract, the increase of the biomass of one or more of the multiple active microorganisms, the increase of the metabolism of the first metabolic substrate, or the improvement of long-term stability.

[0099] As used herein, the term "fermenting microorganism" refers to a microorganism that expresses sufficient amounts of one or more enzymes to catalyze a fermentation reaction in the gastrointestinal niche.

[0100] As used herein, the term "long-term stability" refers to the ability of one or more microorganisms, or a microbial consortium, to remain engrafted and metabolically active in one of more than one niche of the gastrointestinal tract despite temporary or long-term environmental changes in the gastrointestinal niche.

[0101] As used herein, the terms "metabolism," "metabolize," "metabolization," or variants thereof, refer to the biochemical conversion of metabolic substrates to metabolic products. In certain embodiments, metabolism includes isomerization.

[0102] As used herein, the terms "microbes" or "microbiota" refer to microbial organisms, including but not limited to bacteria, archaea, protozoa, and unicellular fungi.

[0103] As used herein, the term "pharmaceutical composition" refers to a combination of an active agent with an active or inert carrier that makes the composition particularly suitable for in vivo or ex vivo therapeutic use.

[0104] As used herein, the term "pharmaceutical acceptable carrier" refers to any of the standard pharmaceutical carriers, such as phosphate buffered saline solution, water, emulsions (e.g., oil / water or water / oil emulsions), and various types of wetting agents. The compositions may also include stabilizers and preservatives. For examples of carriers, stabilizers, and adjuvants, see, for example, Martin, Remington's Pharmaceutical Sciences, 15 th See Ed. Mack Publ. Co., Easton, PA (1975).

[0105] As used herein, "significantly" or "significant" refers to a change or modification of a measurable parameter to a degree that is statistically significant as determined according to an appropriate statistical association test. For example, in certain non-limiting embodiments, a change or modification is significant if it is statistically significant according to, for example, the Student's t-test, chi-square, or Mann-Whitney test.

[0106] As used herein, the term "standardized substrate metabolism assay" refers to an experimental assay known to those of skill in the art that is used to quantitate the amount of a substrate that is converted into a metabolic product.

[0107] As used herein, the term "subject" refers to an organism to be treated by the microbial consortium and compositions described herein. Such organisms preferably include, but are not limited to, mammals (e.g., murines, simians, equines, bovines, porcines, canines, felines, etc.), more preferably humans.

[0108] As used herein, the term "support community" refers to one or more microbial strains that, when the active microorganism is administered, improve one or more characteristics of the active microorganism selected from the group consisting of: gut engraftment, biomass, metabolic substrate metabolism, and long-term stability.

[0109] As used herein, the term "synthetic microorganism" refers to a microorganism that expresses one or more enzymes in sufficient amounts to catalyze the combination of one or more metabolites produced by an active microorganism in the gastrointestinal niche with one or more fermentation products produced by a fermenting microorganism.

[0110] The term "identity" or percent "sequence identity" in the context of two or more nucleic acid or polypeptide sequences refers to two or more sequences or subsequences that, when compared and aligned for maximum correspondence, have a specified percentage of nucleotides or amino acid residues that are the same as measured using one of the sequence comparison algorithms described below (e.g., BLASTP and BLASTN, or other algorithms available to those of skill in the art) or by visual inspection. Depending on the application, the percent "identity" may exist over a region of the sequences being compared, e.g., over a functional domain, or alternatively, over the entire length of the two sequences to be compared.

[0111] For sequence comparison, typically, one sequence serves as the reference sequence with which test sequence is compared.When using sequence comparison algorithm, test and reference sequences are input into computer, sequence coordinates are designated as necessary, and sequence algorithm program parameters are designated.Then, sequence comparison algorithm calculates the percent sequence identity of test sequence with reference sequence based on designated program parameters.

[0112] Optimal sequence alignment for comparison can be performed, for example, by the local homology algorithm of Smith & Waterman, Adv. Appl. Math. 2:482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol. 48:443 (1970), by the search for similarity method of Pearson & Lipman, Proc. Nat'l. Acad. Sci. USA 85:2444 (1988), by computer implementations of these algorithms (GAP, BESTFIT, FASTA and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by visual inspection (see generally Ausubel et al., infra).

[0113] One example of an algorithm that is suitable for determining percent sequence identity and sequence similarity is the BLAST algorithm described in Altschul et al., J. Mol. Biol. 215:403-410 (1990). Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (www.ncbi.nlm.nih.gov / ).

[0114] When used with respect to 16S rRNA sequences, a "sequence identity" of at least 97% indicates that the two microbial strains likely belong to the same species, whereas 16S rRNA sequences with less than 97% sequence identity indicate that the two microbial strains likely belong to different species, and 16S rRNA sequences with less than 95% sequence identity indicate that the two microbial strains likely belong to separate genera (Stackebrandt E., and Goebel, BM, Int J Syst Bact, 44 (1994) 846-849.).

[0115] As used herein, the term "functional equivalent" or "functionally equivalent" refers to microorganisms, microbial consortia, and compositions that share similar or identical roles (e.g., metabolism of oxalate). For example, and without any limitation, two different microbial consortia that can catalyze high concentrations of oxalate are functional equivalents of each other. In certain non-limiting embodiments, functionally equivalent microorganisms, microbial consortia, and compositions can be based on the characteristics outlined in Table 24 (see Examples section).

[0116] Throughout this specification, where compositions are described as having, including, or comprising particular components, or processes and methods are described as having, including, or comprising particular steps, it is further contemplated that there are compositions of the present disclosure that consist essentially of or consist of the stated components, and that there are processes and methods according to the present disclosure that consist essentially of or consist of the stated processing steps.

[0117] Generally, compositions specifying percentages are compositions by weight unless otherwise specified. Further, if a variable is not accompanied by a definition, the previous definition for that variable will control. Biological niche

[0118] Disclosed herein is a microbial consortium for administration to an animal, the microbial consortium comprising a plurality of active microorganisms that metabolize a first metabolic substrate that causes or contributes to disease in the animal.Disclosed herein is a microbial consortium further comprising an effective amount of a support community of microorganisms that metabolize one or more metabolites produced by the plurality of active microorganisms, the one or more metabolites inhibiting the metabolism of the plurality of active microorganisms.These microbial consortiums are advantageous in that when administered to an animal, they have improved characteristics compared to administration of the plurality of active microorganisms alone.The improved characteristics of the microbial consortium include one or more of the following: improved colonization of the digestive tract, increased biomass, increased metabolism of the first metabolic substrate, and improved long-term stability.

[0119] The present disclosure provides microbial consortia that can colonize one or more niches in the gastrointestinal tract, where they can metabolize substrates that cause or contribute to disease in animals. These niches contain specific microbial communities, the composition of which varies depending on several environmental factors, including, but not limited to, the particular physical compartment of the gastrointestinal tract in which they live, the chemical and physicochemical properties of the environment in which they live, the metabolic substrate composition of the environment in which they live, and other co-inhabiting microbial species. Physical Partition

[0120] The digestive tract comprises several physical compartments. For example, the human digestive tract comprises the oral cavity, pharynx, esophagus, stomach, small intestine (duodenum, jejunum, ileum), cecum, large intestine (ascending colon, transverse colon, descending colon), and rectum. In addition, the pancreas, liver, gallbladder, and associated ducts constitute compartments of the human digestive tract. Each of these compartments has, for example, variable anatomical shapes and dimensions, aeration, water content, mucus secretion levels, luminal presence of antimicrobial peptides, and the presence or absence of peristalsis. Furthermore, different digestive tract compartments differ in their pH. In humans, the pH of the oral cavity, upper stomach, lower stomach, duodenum, jejunum, ileum, and colon ranges from 6.5 to 7.5, 4.0 to 6.5, 1.5 to 4.0, 7.0 to 8.5, 4.0 to 7.0, and 4.0 to 7.0, respectively. Compartments of the gut also differ in their oxygen loading levels, and these levels are subject to considerable variation. For example, the luminal oxygen partial pressure in the mouse stomach has been measured to be approximately 58 mmHg, whereas the luminal oxygen partial pressure in the distal sigmoid colon has been measured to be approximately 3 mmHg (He et al., 1999). Oxygen levels in the gut strongly dictate the biochemical pathways utilized by commensal microorganisms. For example, commensal bacteria use aerobic respiration at oxygen concentrations higher than 5 mbar O2, anaerobic respiration between 1-5 mbar O2, and fermentation at O2 concentrations below 1 mbar. The sensitivity of microorganisms to O2 levels, as well as their ability to perform metabolic reactions under aerobic and / or anaerobic conditions, influences which microbial species colonize a particular gut compartment. Metabolic Compartments

[0121] In addition to the various physical and chemical environments that contribute to the gastrointestinal niche, different niches contain different metabolic substrates.

[0122] The metabolic substrates that may be present in the gastrointestinal niche include oxalates, fructans, inulin, glucuronoxylan, arabinoxylan, glucomannan, β-mannan, dextran, starch, arabinan, xyloglucan, galacturonan, β-glucan, galactomannan, rhamnogalacturonan I, rhamnogalacturonan II, arabinogalactan, mucin O-linked glycan, yeast α-mannan, yeast β-glucan, chitin, alginate, porphyrin, laminarin, carrageenan, agarose, alternan, levan, xanthan gum, galactooligosaccharides, hyaluronan, chondroitin sulfate, dermatan sulfate, heparin sulfate, keratan sulfate, phenylalanine, tyrosine, tryptophan, These include, but are not limited to, leucine, valine, isoleucine, glycine, proline, asparagine, glutamine, aspartate, glutamate, cysteine, lysine, arginine, serine, methionine, alanine, arginine, histidine, ornithine, citrulline, carnitine, hydroxyproline, cholic acid, chenodeoxycholic acid, taurochenodeoxycholic acid, glycochenodeoxycholic acid, cholesterol, cinnamic acid, coumaric acid, sinapic acid, ferulic acid, caffeic acid, quinic acid, chlorogenic acid, catechin, epicatechin, gallic acid, pyrogallol, catechol, quercetin, myricetin, campherol, luteolin, apigenin, naringenin, and hesperidin. Consortia

[0123] The present disclosure provides a Consortia comprising a plurality of active microorganisms and an effective amount of a supporting community of microorganisms. In certain embodiments, the Consortia comprises a microbiota listed in any of Tables 1-19. Tables 1-19 are provided below: [Table 1-1] [Table 1-2]

[0124] [Table 2]

[0125]

Table 3

[0126]

Table 4

[0127]

Table 5-1

Table 5-2

[0128]

Table 6-1

Table 6-2

[0129]

Table 7-1

Table 7-2

[0130]

Table 8-1

Table 8-2

[0131]

Table 9-1

Table 9-2

[0132]

Table 10-1

Table 10-2

[0133]

Table 11-1

Table 11-2

[0134]

Table 12-1

Table 12-2

[0135]

Table 13-1

Table 13-2

[0136]

Table 14-1

Table 14-2

[0137]

Table 15-1

Table 15-2

[0138]

Table 16-1

Table 16-2

[0139]

Table 17-1

Table 17-2

[0140]

Table 18

[0141]

Table 19-1

Table 19-2

[0142] In certain embodiments, the Consortia comprises a microbiota listed in Table 1. In certain embodiments, the Consortia comprises a microbiota listed in Table 2. In certain embodiments, the Consortia comprises a microbiota listed in Table 3. In certain embodiments, the Consortia comprises a microbiota listed in Table 4. In certain embodiments, the Consortia comprises a microbiota listed in Table 5. In certain embodiments, the Consortia comprises a microbiota listed in Table 6. In certain embodiments, the Consortia comprises a microbiota listed in Table 7. In certain embodiments, the Consortia comprises a microbiota listed in Table 8. In certain embodiments, the Consortia comprises a microbiota listed in Table 9. In certain embodiments, the Consortia comprises a microbiota listed in Table 10. In certain embodiments, the Consortia comprises a microbiota listed in Table 11. In certain embodiments, the Consortia comprises a microbiota listed in Table 12. In certain embodiments, the Consortia comprises a microbiota listed in Table 13. In certain embodiments, the Consortia comprises a microbiota listed in Table 14. In certain embodiments, the Consortia comprises a microbiota listed in Table 15. In certain embodiments, the Consortia comprises a microbiota listed in Table 16. In certain embodiments, the Consortia comprises a microbiota listed in Table 17. In certain embodiments, the Consortia comprises a microbiota listed in Table 18. In certain embodiments, the Consortia comprises a microbiota listed in Table 19.

[0143] In certain embodiments, the Consortia comprises a microbiota that is at least 90% or at least 95% identical to those listed in Table 1. In certain embodiments, the Consortia comprises a microbiota that is at least 90% or at least 95% identical to those listed in Table 2. In certain embodiments, the Consortia comprises a microbiota that is at least 90% or at least 95% identical to those listed in Table 3. In certain embodiments, the Consortia comprises a microbiota that is at least 90% or at least 95% identical to those listed in Table 4. In certain embodiments, the Consortia comprises a microbiota that is at least 90% or at least 95% identical to those listed in Table 5. In certain embodiments, the Consortia comprises a microbiota that is at least 90% or at least 95% identical to those listed in Table 6. In certain embodiments, the Consortia comprises a microbiota that is at least 90% or at least 95% identical to those listed in Table 7. In certain embodiments, the Consortia comprises a microbiota that is at least 90% or at least 95% identical to that listed in Table 8. In certain embodiments, the Consortia comprises a microbiota that is at least 90% or at least 95% identical to that listed in Table 9. In certain embodiments, the Consortia comprises a microbiota that is at least 90% or at least 95% identical to that listed in Table 10. In certain embodiments, the Consortia comprises a microbiota that is at least 90% or at least 95% identical to that listed in Table 11. In certain embodiments, the Consortia comprises a microbiota that is at least 90% or at least 95% identical to that listed in Table 12. In certain embodiments, the Consortia comprises a microbiota that is at least 90% or at least 95% identical to that listed in Table 13. In certain embodiments, the Consortia comprises a microbiota that is at least 90% or at least 95% identical to that listed in Table 14.In certain embodiments, the Consortia comprises a microbiota that is at least 90% or at least 95% identical to those listed in Table 15. In certain embodiments, the Consortia comprises a microbiota that is at least 90% or at least 95% identical to those listed in Table 16. In certain embodiments, the Consortia comprises a microbiota that is at least 90% or at least 95% identical to those listed in Table 17. In certain embodiments, the Consortia comprises a microbiota that is at least 90% or at least 95% identical to those listed in Table 18. In certain embodiments, the Consortia comprises a microbiota that is at least 90% or at least 95% identical to those listed in Table 19.

[0144] In certain embodiments, the microbial consortium described herein comprises microbial strains with a relative abundance of approximately 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, 5%, 1%, 0.1%, 0.01%, 0.001%, 0.0001%, 0.00001%, or 0.000001% relative to the total microbial consortium. In certain embodiments, the relative abundance of microbial strains is determined by metagenomic sequencing and calculated as the percentage of reads classified as identified microbial strains divided by genome size. In certain embodiments, the relative abundance of microbial strains of the present disclosure is determined by metagenomic shotgun sequencing.

[0145] In certain embodiments, the Consortia comprises microbiota that are at least 90% or at least 95% identical to those listed in Table 22. Table 22 is provided below: [Table 22-1] [Table 22-2] [Table 22-3]

[0146] In certain embodiments, the Consortia comprises a microbiota that is at least 90% or at least 95% identical to those listed in any of Tables 1-19.

[0147] In certain embodiments, the Consortia comprises microbial strains with a relative abundance of approximately 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, 5%, 1%, 0.1%, 0.01%, 0.001%, 0.0001%, 0.00001%, or 0.000001% relative to the total microbial consortium. In certain embodiments, the relative abundance of microbial strains is determined by metagenomic sequencing and calculated as the percentage of reads classified as identified microbial strains divided by genome size. In certain embodiments, the relative abundance of microbial strains of the present disclosure is determined by metagenomic shotgun sequencing. active microorganisms

[0148] The Consortia described herein include a plurality of active microorganisms capable of metabolizing a first metabolic substrate that causes or contributes to a disease in an animal. In certain embodiments, the present disclosure provides a microbial consortium capable of metabolizing a first metabolic substrate at a pH in the range of 4-8. For example, in certain non-limiting embodiments, one or more of the plurality of active microorganisms is / are about 4 to about 8, about 4.2 to about 8, about 4.4 to about 8, about 4.6 to about 8, about 4.8 to about 8, about 5 to about 8, about 5.2 to about 8, about 5.4 to about 8, about 5.6 to about 8, about 5.8 to about 8, about 6 to about 8, about 6.2 to about 8, about 6.4 to about 8, about 6.6 to about 8, about 6.8 to about 8, about 7 to about 8, about 7.2 to about 8, about 7.4 to about 8, about 7.6 to about 8, about 7.8 to about 8, about 4 to about 7, about 4.2 to about 7, about 4.4 to about 7, about 4.6 to about 7, about 4.8 to about 7, about 5 to about 7, about 5.2 The first metabolic substrate can be metabolized at a pH within the range of about 7, about 5.4 to about 7, about 5.6 to about 7, about 5.8 to about 7, about 6 to about 7, about 6.2 to about 7, about 6.4 to about 7, about 6.6 to about 7, about 6.8 to about 7, about 4 to about 6, about 4.2 to about 6, about 4.4 to about 6, about 4.6 to about 6, about 4.8 to about 6, about 5 to about 6, about 5.2 to about 6, about 5.4 to about 6, about 5.6 to about 6, about 5.8 to about 6, about 4 to about 6, about 4.2 to about 6, about 4.4 to about 6, about 4.6 to about 6, about 4.8 to about 6, about 5 to about 6, about 5.2 to about 6, about 5.4 to about 6, about 5.6 to about 6, or about 5.8 to about 6.

[0149] In certain embodiments, the plurality of active microorganisms includes a microbial strain having a first metabolic substrate metabolic activity that is significantly different in a standard substrate metabolic assay performed at two pH values ​​that differ by 1 pH unit and within a pH range of about 4 to about 8. In certain embodiments, the difference between the two pH values ​​is about 1.0, about 1.1, about 1.2, about 1.3, about 1.4, about 1.5, about 1.6, about 1.7, about 1.8, about 1.9, about 2.0, about 2.1, about 2.2, about 2.3, about 2.4, about 2.5, about 2.6, about 2.7, about 2.8, about 2.9, about 3.0, about 3.2, about 3.3, about 3.4, about 3.5, about 3.6, about 3.7, about 3.8, about 3.9, or about 4.0 pH units. For example, in certain non-limiting embodiments, a microbial strain has a first metabolic substrate metabolic activity that is significantly different at pH 4 and pH 8, pH 5 and pH 8, pH 6 and pH 8, pH 7 and pH 8, pH 4 and pH 7, pH 5 and pH 7, pH 6 and pH 7, pH 4 and pH 6, pH 5 and pH 6, or pH 4 and pH 5 in a standard substrate metabolic assay.

[0150] As used herein, "lower pH" or "low pH" refers to a pH in a standardized substrate metabolism assay that is lower in value compared to another pH value. For example, a standardized substrate metabolism assay performed at pH 4.5 has a lower pH compared to a preformed standardized substrate metabolism assay at pH 7.5. As used herein, "higher pH" refers to a pH in a standardized substrate metabolism assay that is higher in value compared to another pH value. For example, a preformed standardized substrate metabolism assay at pH 7.5 has a higher pH compared to a standardized substrate metabolism assay performed at pH 4.5.

[0151] As used herein, "higher first metabolic substrate metabolic activity" means either a higher first metabolic substrate metabolic activity of a microbial strain compared to the first metabolic substrate metabolic activity of the same microbial strain under different conditions, and / or a higher first metabolic substrate metabolic activity of a microbial strain compared to the first metabolic substrate metabolic activity of a different microbial strain under the same conditions.

[0152] In certain embodiments, the plurality of active microorganisms comprises two microbial strains with significantly different first metabolic substrate metabolic activity.For example, in certain non-limiting embodiments, one of the plurality of active microorganisms has a significantly higher first metabolic substrate metabolic activity at lower pH compared to the first metabolic substrate metabolic activity of another microbial strain of the plurality of active microorganisms at the same lower pH.In certain embodiments, one of the plurality of active microorganisms has a significantly higher first metabolic substrate metabolic activity at pH 4.0, 4.5, 5.0, 5.5, 6.0 or 6.5 compared to the first metabolic substrate metabolic activity of another microbial strain of the plurality of active microorganisms at pH 4.0, 4.5, 5.0, 5.5, 6.0 or 6.5, respectively.In certain embodiments, one of the plurality of active microorganisms has a significantly higher first metabolic substrate metabolic activity at higher pH compared to the first metabolic substrate metabolic activity of another microbial strain of the plurality of active microorganisms at the same higher pH. In certain embodiments, one of the plurality of active microorganisms has a significantly higher first metabolic substrate metabolic activity at pH 7.5, 7.6, 7.7, 7.8, 7.9 or 8.0 compared to the first metabolic substrate metabolic activity of another microbial strain of the plurality of active microorganisms at pH 7.5, 7.6, 7.7, 7.8, 7.9 or 8.0, respectively.

[0153] In certain embodiments, one of the plurality of active microorganisms has a significantly higher first metabolic substrate metabolic activity at lower pH compared to its first metabolic substrate metabolic activity at higher pH.For example, in some embodiments, one of the plurality of active microorganisms has a significantly higher first metabolic substrate metabolic activity at pH 4.0, 4.5, 5.0, 5.5, 6.0 or 6.5 than it has at pH 7.5, 7.6, 7.7, 7.8, 7.9 or 8.0.In certain embodiments, one of the plurality of active microorganisms has a significantly higher first metabolic substrate metabolic activity at higher pH compared to its first metabolic substrate metabolic activity at lower pH. For example, in some embodiments, one of the plurality of active microorganisms has a significantly higher first metabolic substrate metabolic activity at pH 7.5, 7.6, 7.7, 7.8, 7.9 or 8.0 than it has at pH 4.0, 4.5, 5.0, 5.5, 6.0 or 6.5.

[0154] In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at a lower pH, and another microorganism having a higher first metabolic substrate metabolic activity at a higher pH. For example, in certain non-limiting embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 4.0, and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.5. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 4.0, and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.6. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 4.0, and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.7. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 4.0, and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.8. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 4.0 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.9. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 4.0 and another microorganism having a higher first metabolic substrate metabolic activity at pH 8.0. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 4.5 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.5. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 4.5 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.6. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 4.5 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.7. In certain embodiments, the plurality of active microorganisms includes an active microorganism having a higher first metabolic substrate metabolic activity at pH 4.5 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.8.In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 4.5 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.9. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 4.5 and another microorganism having a higher first metabolic substrate metabolic activity at pH 8.0. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 5.0 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.5. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 5.0 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.6. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 5.0 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.7. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 5.0 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.8. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 5.0 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.9. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 5.0 and another microorganism having a higher first metabolic substrate metabolic activity at pH 8.0. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 5.5 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.5. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 5.5 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.6. In certain embodiments, the plurality of active microorganisms includes an active microorganism having a higher first metabolic substrate metabolic activity at pH 5.5 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.7.In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 5.5 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.8. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 5.5 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.9. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 5.5 and another microorganism having a higher first metabolic substrate metabolic activity at pH 8.0. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 6.0 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.5. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 6.0 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.6. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 6.0 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.7. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 6.0 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.8. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 6.0 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.9. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 6.0 and another microorganism having a higher first metabolic substrate metabolic activity at pH 8.0. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 6.5 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.5. In certain embodiments, the plurality of active microorganisms includes an active microorganism having a higher first metabolic substrate metabolic activity at pH 6.5 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.6.In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 6.5 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.7. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 6.5 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.8. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 6.5 and another microorganism having a higher first metabolic substrate metabolic activity at pH 7.9. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher first metabolic substrate metabolic activity at pH 6.5 and another microorganism having a higher first metabolic substrate metabolic activity at pH 8.0.

[0155] In certain embodiments, the plurality of active microorganisms comprises a microorganism strain whose first metabolic substrate metabolic activity in a standard substrate metabolic assay carried out at a first metabolic substrate concentration is significantly different from its first metabolic substrate metabolic activity in a standard substrate metabolic assay carried out at a different first metabolic substrate concentration, and the difference between the two first metabolic substrate concentrations is within a 100-fold range.In certain embodiments, the difference between the two first metabolic substrate concentrations is about 1.2-fold.For example, in certain non-limiting embodiments, the difference between the two first metabolic substrate concentrations is at least about 1.2-fold, about 1.4-fold, about 1.6-fold, about 1.8-fold, about 2.0-fold, about 4-fold, about 6-fold, about 8-fold, about 10-fold, about 20-fold, about 30-fold, about 40-fold, about 50-fold, about 60-fold, about 70-fold, about 80-fold, about 90-fold, or about 100-fold or more.

[0156] As used herein, a "lower first metabolic substrate concentration" refers to a substrate concentration in a standardized substrate metabolic assay that is lower in value compared to another substrate concentration. As used herein, a "higher first metabolic substrate concentration" refers to a substrate concentration in a standardized substrate metabolic assay that is higher in value compared to another substrate concentration.

[0157] In certain embodiments, the plurality of active microorganisms comprises two microbial strains with significantly different first metabolic substrate metabolic activity.For example, in certain non-limiting embodiments, one of the plurality of active microorganisms has a significantly higher first metabolic substrate metabolic activity at a lower first metabolic substrate concentration, compared with the first metabolic substrate metabolic activity of another microbial strain of the plurality of active microorganisms at the same lower first metabolic substrate concentration.In certain embodiments, one of the plurality of active microorganisms has a significantly higher first metabolic substrate metabolic activity at a higher first metabolic substrate concentration, compared with the first metabolic substrate metabolic activity of another microbial strain of the plurality of active microorganisms at the same higher first metabolic substrate concentration.

[0158] In certain embodiments, one of the plurality of active microorganisms has a significantly higher first metabolic substrate metabolic activity at a lower first metabolic substrate concentration compared to its first metabolic substrate metabolic activity at a higher first metabolic substrate concentration.In certain embodiments, one of the plurality of active microorganisms has a significantly higher first metabolic substrate metabolic activity at a higher first metabolic substrate concentration compared to its first metabolic substrate metabolic activity at a lower first metabolic substrate concentration.

[0159] In certain embodiments, the plurality of active microorganisms comprises an active microorganism that has a higher first metabolic substrate metabolic activity at a lower first metabolic substrate concentration, and another microorganism that has a higher first metabolic substrate metabolic activity at a higher first metabolic substrate concentration.For example, in certain non-limiting embodiments, the difference between the lower first metabolic substrate concentration and the higher first metabolic substrate concentration is at least about 1.2 times, about 1.4 times, about 1.6 times, about 1.8 times, about 2.0 times, about 4 times, about 6 times, about 8 times, about 10 times, about 20 times, about 30 times, about 40 times, about 50 times, about 60 times, about 70 times, about 80 times, about 90 times, or about 100 times or more.

[0160] In certain embodiments, the plurality of active microorganisms comprises two microbial strains with significantly different growth rates.For example, in certain non-limiting embodiments, one of the plurality of active microorganisms has a significantly higher growth rate at a lower pH than the growth rate of another microbial strain of the plurality of active microorganisms at the same lower pH.In certain embodiments, one of the plurality of active microorganisms has a significantly higher growth rate at pH 4.0, 4.5, 5.0, 5.5, 6.0 or 6.5 than the growth rate of another microbial strain of the plurality of active microorganisms at pH 4.0, 4.5, 5.0, 5.5, 6.0 or 6.5, respectively.In certain embodiments, one of the plurality of active microorganisms has a significantly higher growth rate at a higher pH than the growth rate of another microbial strain of the plurality of active microorganisms at the same higher pH. In certain embodiments, one of the plurality of active microorganisms has a significantly higher growth rate at pH 7.5, 7.6, 7.7, 7.8, 7.9 or 8.0 compared to the growth rate of another microbial strain of the plurality of active microorganisms at pH 7.5, 7.6, 7.7, 7.8, 7.9 or 8.0, respectively.

[0161] In certain embodiments, one of the active microorganisms has a significantly higher growth rate at lower pH than its growth rate at higher pH.For example, in some embodiments, one of the active microorganisms has a significantly higher growth rate at pH 4.0, 4.5, 5.0, 5.5, 6.0 or 6.5 than its growth rate at pH 7.5, 7.6, 7.7, 7.8, 7.9 or 8.0.In certain embodiments, one of the active microorganisms has a significantly higher growth rate at higher pH than its growth rate at lower pH.For example, in some embodiments, one of the active microorganisms has a significantly higher growth rate at pH 7.5, 7.6, 7.7, 7.8, 7.9 or 8.0 than its growth rate at pH 4.0, 4.5, 5.0, 5.5, 6.0 or 6.5.

[0162] In certain embodiments, the plurality of active microorganisms comprises a microbial strain that has a significantly higher growth rate when cultured in a medium containing a certain concentration of a first metabolic substrate, compared with the growth rate of another microbial strain of the plurality of active microorganisms cultured in the same medium containing the same first metabolic substrate concentration.In certain embodiments, the difference between the two growth rates is at least about 0.2 times, at least about 0.4 times, at least about 0.6 times, at least about 0.8 times, at least about 1.0 times, at least about 1.2 times, at least about 1.4 times, at least about 1.6 times, at least about 1.8 times, or at least about 2.0 times.

[0163] In certain embodiments, the first metabolic substrate may be selected from, but is not limited to, oxalate and bile acids (eg, lithocholic acid (LCA), deoxycholic acid (DCA)).

[0164] In certain embodiments, the present disclosure provides a microbial consortium comprising a plurality of active microorganisms capable of metabolizing a first metabolic substrate to one or more than one metabolite. For example, in certain non-limiting embodiments, the one or more metabolites may be selected from, but are not limited to, formate, CO2, and secondary bile acids (e.g., 3-oxo-deoxycholic acid (3oxoDCA), 3-oxo-lithocholic acid (3oxoLCA), isolithocholic acid (isoLCA), or isodeoxycholic acid (isoDCA)). In certain embodiments, the plurality of active microorganisms may comprise 2 to 200 microbial strains. For example, in certain non-limiting embodiments, the microbial consortium comprises between 2 and 10, between 2 and 15, between 2 and 20, between 2 and 25, between 2 and 30, between 2 and 35, between 2 and 40, between 2 and 45, between 2 and 50, between 2 and 75, between 2 and 100, between 2 and 125, between 2 and 150, between 2 and 175, or between 2 and 200 active microbial strains. In certain embodiments, the plurality of active microorganisms may comprise between 2 and 20 microbial strains. Oxalate-metabolizing active microorganisms

[0165] The Consortia described herein comprises a plurality of active microorganisms that metabolize oxalate. In certain embodiments, each of the plurality of active microorganisms that metabolize oxalate expresses a sufficient amount of one or more enzymes involved in oxalate metabolism. For example, in certain non-limiting embodiments, one or more active microorganisms express formyl-CoA transferase (Frc), oxalate-formate exchanger (OxIT), and oxalyl-CoA decarboxylase (e.g., OxC), and / or oxalate decarboxylase (e.g., OxD).

[0166] In certain embodiments, the plurality of active microorganisms that metabolize oxalate comprises between 2 and 20 oxalate metabolizing microbial strains. In certain embodiments, the plurality of active microorganisms that metabolize oxalate comprises between 2 and 5 oxalate metabolizing microbial strains. In certain embodiments, the plurality of active microorganisms that metabolize oxalate comprises between 2 and 7 oxalate metabolizing microbial strains. In certain embodiments, the plurality of active microorganisms that metabolize oxalate comprises between 2 and 7 oxalate metabolizing microbial strains. In certain embodiments, the plurality of active microorganisms that metabolize oxalate comprises more than 20 oxalate metabolizing microbial strains. In certain embodiments, the plurality of active microorganisms comprises three strains of oxalate metabolizing microorganisms. In certain embodiments, two or more of the active microorganisms are different strains of the same species.

[0167] In certain embodiments, the multiple active microorganisms that metabolize oxalate include, but are not limited to, Oxalobacter formigenes, Bifidobacterium sp., Bifidobacterium dentium, Dialister invisus, Lactobacillus acidophilus, Lactobacillus gasseri, Lactobacillus helveticus, Lactobacillus reuteri, Eggerthella lenta, Lactobacillus rhamnosus, Enterococcus faecalis, Enterococcus gallinarum, Enterococcus faecium, Providencia rettgeri, Streptococcus thermophilus, Lactobacillus plantarum, Lactobacillus casei, Lactobacillus salivarius, Lactobacillus johnsii, Bifidobacterium infantis, Bifidobacterium animalis, Clostridium sporogenes, Leuconostoc lactis, or Leuconostoc mesenteroides.

[0168] In certain embodiments, the Consortia described herein comprises three strains of Oxalobacter formigenes. In certain embodiments, the Consortia described herein comprises three strains of Oxalobacter formigenes, each with different phenotypic characteristics. In certain embodiments, the Consortia described herein comprises three strains of Oxalobacter formigenes, one strain is low pH tolerant, one strain is high oxalate tolerant, and one strain has a high growth rate. In certain embodiments, the low pH tolerance is approximately pH 5. In certain embodiments, the high oxalate tolerance is approximately 150 mM. In certain embodiments, the high oxalate tolerance is approximately 15 mM.

[0169] In certain embodiments, the plurality of active microorganisms includes an Oxalobacter formigenes strain having a 16S sequence that is at least about 80% identical to the nucleotide sequence set forth in SEQ ID NO: 42, SEQ ID NO: 79, or SEQ ID NO: 146. In certain embodiments, the plurality of active microorganisms includes an Oxalobacter formigenes strain having a 16S sequence that is at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identical to the nucleotide sequence set forth in SEQ ID NO: 42, SEQ ID NO: 79, or SEQ ID NO: 146. In certain embodiments, the plurality of active microorganisms includes three Oxalobacter formigenes strains, a first, a second, and a third having respective 16S sequences that are identical to the nucleotide sequence set forth in SEQ ID NO: 42, SEQ ID NO: 79, or SEQ ID NO: 146. In certain embodiments, the plurality of active microorganisms comprises three Oxalobacter formigenes strains, the first, second and third of which have respective 16S sequences that are at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identical to the nucleotide sequence set forth in SEQ ID NO: 42, SEQ ID NO: 79 or SEQ ID NO: 146. In certain embodiments, the plurality of active microorganisms comprises three Oxalobacter formigenes strains, the first, second and third of which have respective 16S sequences that are at least about 97% identical to the nucleotide sequence set forth in SEQ ID NO: 42, SEQ ID NO: 79 or SEQ ID NO: 146.

[0170] In some embodiments, the plurality of active microorganisms includes an Oxalobacter formigenes strain having a 16S sequence at least about 80% identical to the nucleotide sequence set forth in SEQ ID NO:42, and an Oxalobacter formigenes strain having a 16S sequence at least about 80% identical to the nucleotide sequence set forth in SEQ ID NO:79. In certain embodiments, the plurality of active microorganisms includes an Oxalobacter formigenes strain having a 16S sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identical to the nucleotide sequence set forth in SEQ ID NO:42, and an Oxalobacter formigenes strain having a 16S sequence at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identical to the nucleotide sequence set forth in SEQ ID NO:79.

[0171] In some embodiments, the plurality of active microorganisms includes an Oxalobacter formigenes strain having a 16S sequence at least about 80% identical to the nucleotide sequence set forth in SEQ ID NO:42, and an Oxalobacter formigenes strain having a 16S sequence at least about 80% identical to the nucleotide sequence set forth in SEQ ID NO:146. In certain embodiments, the plurality of active microorganisms includes an Oxalobacter formigenes strain having a 16S sequence that is at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identical to the nucleotide sequence set forth in SEQ ID NO:42, and an Oxalobacter formigenes strain having a 16S sequence that is at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identical to the nucleotide sequence set forth in SEQ ID NO:146.

[0172] In some embodiments, the plurality of active microorganisms includes an Oxalobacter formigenes strain having a 16S sequence that is at least 80% identical to the nucleotide sequence set forth in SEQ ID NO:79, and an Oxalobacter formigenes strain having a 16S sequence that is at least about 80% identical to the nucleotide sequence set forth in SEQ ID NO:146. In certain embodiments, the plurality of active microorganisms includes an Oxalobacter formigenes strain having a 16S sequence that is at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identical to the nucleotide sequence set forth in SEQ ID NO:79, and an Oxalobacter formigenes strain having a 16S sequence that is at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identical to the nucleotide sequence set forth in SEQ ID NO:146.

[0173] As used herein, "substantially metabolize oxalate," "substantially metabolize oxalate," and variants thereof refer to a statistically significant reduction in the amount of oxalate in an in vitro assay. In certain embodiments, one or more of the plurality of active microorganisms is capable of substantially metabolizing oxalate at a pH within the range of 4-8. In certain embodiments, one or more of the plurality of active microorganisms is / are from about 4 to about 8, from about 4.2 to about 8, from about 4.4 to about 8, from about 4.6 to about 8, from about 4.8 to about 8, from about 5 to about 8, from about 5.2 to about 8, from about 5.4 to about 8, from about 5.6 to about 8, from about 5.8 to about 8, from about 6 to about 8, from about 6.2 to about 8, from about 6.4 to about 8, from about 6.6 to about 8, from about 6.8 to about 8, from about 7 to about 8, from about 7.2 to about 8, from about 7.4 to about 8, from about 7.6 to about 8, from about 7.8 to about 8, from about 4 to about 7, from about 4.2 to about 7, from about 4.4 to about 7, from about 4.6 to about 7, from about 4.8 to about 7, from about 5 to about 7, from about 5.2 to about 7, Oxalate can be metabolized at a pH within the range of about 5.4 to about 7, about 5.6 to about 7, about 5.8 to about 7, about 6 to about 7, about 6.2 to about 7, about 6.4 to about 7, about 6.6 to about 7, about 6.8 to about 7, about 4 to about 6, about 4.2 to about 6, about 4.4 to about 6, about 4.6 to about 6, about 4.8 to about 6, about 5 to about 6, about 5.2 to about 6, about 5.4 to about 6, about 5.6 to about 6, about 5.8 to about 6, about 4 to about 6, about 4.2 to about 6, about 4.4 to about 6, about 4.6 to about 6, about 4.8 to about 6, about 5 to about 6, about 5.2 to about 6, about 5.4 to about 6, about 5.6 to about 6, or about 5.8 to about 6.

[0174] In certain embodiments, the plurality of active microorganisms comprises a microbial strain that has significantly different oxalate metabolic activities in a standard oxalate metabolic assay performed at two pH values ​​that differ by at least 1 pH unit and within a pH range of 4 to 8. In certain embodiments, a microbial strain has significantly different oxalate metabolic activities in a standard oxalate metabolic assay at pH 4 and pH 8, pH 5 and pH 8, pH 6 and pH 8, pH 7 and pH 8, pH 4 and pH 7, pH 5 and pH 7, pH 6 and pH 7, pH 4 and pH 6, pH 5 and pH 6, or pH 4 and pH 5.

[0175] In certain embodiments, oxalate metabolic activity is detected using a standard oxalate metabolic assay. In certain embodiments, oxalate metabolic activity is detected using a colorimetric enzyme assay that measures the activity of oxalate oxidase. In certain embodiments, the relative change in oxalate abundance in the culture medium inoculated with the microbial strain is measured using a commercially available oxalate assay kit (e.g., Sigma-Aldrich, catalog number MAK315). In certain embodiments, oxalate metabolic activity is detected using liquid chromatography-mass spectrometry (LC-MS / MS). In certain embodiments, the relative change in oxalate abundance is compared between the amount of oxalate present at the start of inoculation (i.e., t=0) and the amount of oxalate present after about 2 hours, about 4 hours, about 6 hours, about 8 hours, about 10 hours, about 12 hours, about 14 hours, about 16 hours, about 18 hours, about 24 hours, about 30 hours, about 36 hours, about 48 hours, about 60 hours, about 72 hours, about 84 hours, about 96 hours, about 120 hours, or about 144 hours of incubation.

[0176] As used herein, "higher oxalate metabolic activity" means either a higher oxalate metabolic activity of a microbial strain compared to the oxalate metabolic activity of the same microbial strain under different conditions, and / or a higher oxalate metabolic activity of a microbial strain compared to the oxalate metabolic activity of a different microbial strain under the same conditions.

[0177] In certain embodiments, the plurality of active microorganisms comprises two microbial strains with significantly different oxalate metabolic activity.In certain embodiments, one of the plurality of active microorganisms has a significantly higher oxalate metabolic activity at lower pH compared to the oxalate metabolic activity of another microbial strain of the plurality of active microorganisms at the same lower pH.In certain embodiments, one of the plurality of active microorganisms has a significantly higher oxalate metabolic activity at pH 4.0, 4.5, 5.0, 5.5, 6.0 or 6.5 compared to the oxalate metabolic activity of another microbial strain of the plurality of active microorganisms at pH 4.0, 4.5, 5.0, 5.5, 6.0 or 6.5, respectively.In certain embodiments, one of the plurality of active microorganisms has a significantly higher oxalate metabolic activity at higher pH compared to the oxalate metabolic activity of another microbial strain of the plurality of active microorganisms at the same higher pH. In certain embodiments, one of the plurality of active microorganisms has a significantly higher oxalate metabolic activity at pH 7.5, 7.6, 7.7, 7.8, 7.9 or 8.0 compared to the oxalate metabolic activity of another microbial strain of the plurality of active microorganisms at pH 7.5, 7.6, 7.7, 7.8, 7.9 or 8.0, respectively.

[0178] In certain embodiments, one of the plurality of active microorganisms has a significantly higher oxalate metabolic activity at lower pH than its oxalate metabolic activity at higher pH.In certain embodiments, one of the plurality of active microorganisms has a significantly higher oxalate metabolic activity at pH 4.0, 4.5, 5.0, 5.5, 6.0 or 6.5 than its oxalate metabolic activity at pH 7.5, 7.6, 7.7, 7.8, 7.9 or 8.0.In certain embodiments, one of the plurality of active microorganisms has a significantly higher oxalate metabolic activity at higher pH than its oxalate metabolic activity at lower pH.In certain embodiments, one of the plurality of active microorganisms has a significantly higher oxalate metabolic activity at pH 7.5, 7.6, 7.7, 7.8, 7.9 or 8.0 than its oxalate metabolic activity at pH 4.0, 4.5, 5.0, 5.5, 6.0 or 6.5.

[0179] In certain embodiments, the plurality of active microorganisms comprises an active microorganism with a higher oxalate metabolic activity at a lower pH and another microorganism with a higher oxalate metabolic activity at a higher pH. In certain embodiments, the plurality of active microorganisms comprises an active microorganism with a higher oxalate metabolic activity at pH 4.0 and another microorganism with a higher oxalate metabolic activity at pH 7.5. In certain embodiments, the plurality of active microorganisms comprises an active microorganism with a higher oxalate metabolic activity at pH 4.0 and another microorganism with a higher oxalate metabolic activity at pH 7.6. In certain embodiments, the plurality of active microorganisms comprises an active microorganism with a higher oxalate metabolic activity at pH 4.0 and another microorganism with a higher oxalate metabolic activity at pH 7.7. In certain embodiments, the plurality of active microorganisms comprises an active microorganism with a higher oxalate metabolic activity at pH 4.0 and another microorganism with a higher oxalate metabolic activity at pH 7.8. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 4.0 and another microorganism having a higher oxalate metabolic activity at pH 7.9. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 4.0 and another microorganism having a higher oxalate metabolic activity at pH 8.0. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 4.5 and another microorganism having a higher oxalate metabolic activity at pH 7.5. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 4.5 and another microorganism having a higher oxalate metabolic activity at pH 7.6. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 4.5 and another microorganism having a higher oxalate metabolic activity at pH 7.7. In certain embodiments, the plurality of active microorganisms includes an active microorganism that has a higher oxalate metabolic activity at pH 4.5 and another microorganism that has a higher oxalate metabolic activity at pH 7.8.In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 4.5 and another microorganism having a higher oxalate metabolic activity at pH 7.9. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 4.5 and another microorganism having a higher oxalate metabolic activity at pH 8.0. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 5.0 and another microorganism having a higher oxalate metabolic activity at pH 7.5. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 5.0 and another microorganism having a higher oxalate metabolic activity at pH 7.6. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 5.0 and another microorganism having a higher oxalate metabolic activity at pH 7.7. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 5.0 and another microorganism having a higher oxalate metabolic activity at pH 7.8. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 5.0 and another microorganism having a higher oxalate metabolic activity at pH 7.9. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 5.0 and another microorganism having a higher oxalate metabolic activity at pH 8.0. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 5.5 and another microorganism having a higher oxalate metabolic activity at pH 7.5. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 5.5 and another microorganism having a higher oxalate metabolic activity at pH 7.6. In certain embodiments, the plurality of active microorganisms includes an active microorganism having a higher oxalate metabolic activity at pH 5.5 and another microorganism having a higher oxalate metabolic activity at pH 7.7.In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 5.5 and another microorganism having a higher oxalate metabolic activity at pH 7.8. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 5.5 and another microorganism having a higher oxalate metabolic activity at pH 7.9. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 5.5 and another microorganism having a higher oxalate metabolic activity at pH 8.0. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 6.0 and another microorganism having a higher oxalate metabolic activity at pH 7.5. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 6.0 and another microorganism having a higher oxalate metabolic activity at pH 7.6. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 6.0 and another microorganism having a higher oxalate metabolic activity at pH 7.7. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 6.0 and another microorganism having a higher oxalate metabolic activity at pH 7.8. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 6.0 and another microorganism having a higher oxalate metabolic activity at pH 7.9. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 6.0 and another microorganism having a higher oxalate metabolic activity at pH 8.0. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 6.5 and another microorganism having a higher oxalate metabolic activity at pH 7.5. In certain embodiments, the plurality of active microorganisms includes an active microorganism that has a higher oxalate metabolic activity at pH 6.5 and another microorganism that has a higher oxalate metabolic activity at pH 7.6.In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 6.5 and another microorganism having a higher oxalate metabolic activity at pH 7.7. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 6.5 and another microorganism having a higher oxalate metabolic activity at pH 7.8. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 6.5 and another microorganism having a higher oxalate metabolic activity at pH 7.9. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at pH 6.5 and another microorganism having a higher oxalate metabolic activity at pH 8.0.

[0180] In certain embodiments, one or more of the plurality of active microorganisms is capable of substantially metabolizing oxalate at an oxalate concentration of about 0.75 mM to about 40 mM oxalate. In certain embodiments, one or more of the plurality of active microorganisms is capable of substantially metabolizing oxalate at an oxalate concentration of about 0.75 mM to about 40 mM, about 1 mM to about 40 mM, about 2.5 mM to about 40 mM, about 5 mM to about 40 mM, about 7.5 mM to about 40 mM, about 10 mM to about 40 mM, about 15 mM to about 40 mM, about 20 mM to about 40 mM, about 25 mM to about 40 mM, about 30 mM to about 40 mM, about 0.75 mM to about 30 mM, about 0.5 mM to about 40 mM, about 0.6 mM to about 40 mM, about 0.75 mM to about 40 mM, about 0.8 mM to about 40 mM, about 0.9 ... mM, about 1 mM to about 30 mM, about 2.5 mM to about 30 mM, about 5 mM to about 30 mM, about 7.5 mM to about 30 mM, about 10 mM to about 30 mM, about 15 mM to about 30 mM, about 20 mM to about 30 mM, about 25 mM to about 30 mM, about 0.75 mM to about 25 mM, about 1 mM to about 25 mM, about 2.5 mM to about 25 mM, about 5 mM to about 25 mM, about 7.5 mM to about 25 mM, about 10 mM to about 30 mM about 25 mM, about 15 mM to about 25 mM, about 20 mM to about 25 mM, about 0.75 mM to about 20 mM, about 1 mM to about 20 mM, about 2.5 mM to about 20 mM, about 5 mM to about 20 mM, about 7.5 mM to about 20 mM, about 10 mM to about 20 mM, about 15 mM to about 20 mM, about 0.75 mM to about 15 mM, about 1 mM to about 15 mM, about 2.5 mM to about 15 mM, about 5 mM to about 15 mM, about The oxalate can be substantially metabolized at oxalate concentrations within the range of 7.5 mM to about 15 mM, about 10 mM to about 15 mM, about 0.75 mM to about 10 mM, about 1 mM to about 10 mM, about 2.5 mM to about 10 mM, about 5 mM to about 10 mM, about 7.5 mM to about 10 mM, about 0.75 mM to about 5 mM, about 1 mM to about 5 mM, about 2.5 mM to about 5 mM, or about 0.75 mM to about 1 mM.

[0181] In certain embodiments, the active microorganisms include a microorganism strain whose oxalate metabolic activity in a standard in vitro oxalate metabolic assay at a certain oxalate concentration is significantly different from its oxalate metabolic activity in a standard in vitro oxalate metabolic assay performed at a different oxalate concentration, and the difference between the two oxalate concentrations is within 100-fold.In certain embodiments, the microorganism strain has an oxalate metabolic activity of about 0.75 mM oxalate and about 40 mM oxalate, about 1 mM and about 40 mM, about 2.5 mM and about 40 mM, about 5 mM and about 40 mM, about 7.5 mM and about 40 mM, about 10 mM and about 40 mM, about 15 mM and about 40 mM, about 20 mM and about 40 mM, about 25 mM and about 40 mM, about 30 mM and about 40 mM, about 0.75 mM and about 30 mM, about 1 mM and about 30 mM, about 2.5 mM and about 30 mM, about 5 mM and about 30 mM, about 7.5 mM and about 30 mM, about 10 mM and about 30 mM, about 15 mM and about 30 mM, about 20 mM and about 30 mM, about 25 mM and about 30 mM, about 0.75 mM and about 25 mM, about 1 mM and about 25 mM, about 2.5 mM and about 25 mM, about 5 mM and about 25 mM, about 7.5 mM and about 25 mM, about 10 mM and about 25 mM, about 15 mM and about 25 mM, about 20 mM and about 25 mM, about 0.75 mM and about 20 mM, about 1 mM and about 20 mM, about 2.5 mM and about 20 mM, about 5 mM and about 20 mM, about 7.5 mM and about 20 mM, about 10 mM and about 20 mM, about 15 mM and about 20 mM, about 0.75 mM and about 15 mM, about 1 mM and about 15 mM, about 2.5 mM and about 15 mM, about 5 mM and about 15 mM, about 7.5 mM and about 1 In a standard oxalate metabolism assay performed at 5 mM, about 10 mM and about 15 mM, about 0.75 mM and about 10 mM, about 1 mM and about 10 mM, about 2.5 mM and about 10 mM, about 5 mM and about 10 mM, about 7.5 mM and about 10 mM, about 0.75 mM and about 5 mM, about 1 mM and about 5 mM, about 2.5 mM and about 5 mM, or about 0.75 mM and about 1 mM,

[0182] In certain embodiments, the plurality of active microorganisms comprises two microbial strains with significantly different oxalate metabolic activity.In certain embodiments, one of the plurality of active microorganisms has a significantly higher oxalate metabolic activity at a lower oxalate concentration compared to the oxalate metabolic activity of another microbial strain of the plurality of active microorganisms at the same lower oxalate concentration.In certain embodiments, one of the plurality of active microorganisms has a significantly higher oxalate metabolic activity at an oxalate concentration of about 0.75mM, about 1mM, about 2.5mM, about 5mM, or about 7.5mM compared to the oxalate metabolic activity of another microbial strain of the plurality of active microorganisms at an oxalate concentration of about 0.75mM, about 1mM, about 2.5mM, about 5mM, or about 7.5mM, respectively.In certain embodiments, one of the plurality of active microorganisms has a significantly higher oxalate metabolic activity at a higher oxalate concentration compared to the oxalate metabolic activity of another microbial strain of the plurality of active microorganisms at the same higher oxalate concentration. In certain embodiments, one of the plurality of active microorganisms has a significantly higher oxalate metabolic activity at an oxalate concentration of about 15 mM, about 20 mM, about 25 mM, about 30 mM, or about 40 mM compared to the oxalate metabolic activity of another microbial strain of the plurality of active microorganisms at an oxalate concentration of about 15 mM, about 20 mM, about 25 mM, about 30 mM, or about 40 mM, respectively.

[0183] In certain embodiments, one of the plurality of active microorganisms has a significantly higher oxalate metabolic activity at a lower oxalate concentration than its oxalate metabolic activity at a higher oxalate concentration.In certain embodiments, one of the plurality of active microorganisms has a significantly higher oxalate metabolic activity at about 0.75mM, about 1mM, about 2.5mM, about 5mM, or about 7.5mM oxalate than its oxalate metabolic activity at about 15mM, about 20mM, about 25mM, about 30mM, or about 40mM.In certain embodiments, one of the plurality of active microorganisms has a significantly higher oxalate metabolic activity at a higher oxalate concentration than its oxalate metabolic activity at a lower oxalate concentration. In certain embodiments, one of the plurality of active microorganisms has significantly higher oxalate metabolic activity at about 15 mM, about 20 mM, about 25 mM, about 30 mM, or about 40 mM oxalate than it has at about 0.75 mM, about 1 mM, about 2.5 mM, about 5 mM, or about 7.5 mM oxalate.

[0184] In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at a lower oxalate concentration, and another active microorganism having a higher oxalate metabolic activity at a higher oxalate concentration. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 0.75 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 40 mM oxalate. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 1 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 40 mM oxalate. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 2.5 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 40 mM oxalate. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 5 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 40 mM oxalate. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 7.5 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 40 mM oxalate.In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 0.75 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 30 mM oxalate.In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 1 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 30 mM oxalate.In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 2.5 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 30 mM oxalate.In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 5 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 30 mM oxalate.In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 7.5 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 30 mM oxalate.In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 0.75 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 25 mM oxalate.In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 1 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 25 mM oxalate. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 2.5 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 25 mM oxalate.In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 5 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 25 mM oxalate.In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 7.5 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 25 mM oxalate.In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 0.75 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 20 mM oxalate. In certain embodiments, the plurality of active microorganisms includes an active microorganism having a higher oxalate metabolic activity at about 1 mM oxalate and another active microorganism having a higher oxalate metabolic activity at about 20 mM oxalate.In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 2.5 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 20 mM oxalate.In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 5 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 20 mM oxalate.In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 7.5 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 20 mM oxalate.In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 0.75 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 15 mM oxalate. In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 1 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 15 mM oxalate.In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 2.5 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 15 mM oxalate.In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 5 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 15 mM oxalate.In certain embodiments, the plurality of active microorganisms comprises an active microorganism having a higher oxalate metabolic activity at about 7.5 mM oxalate, and another active microorganism having a higher oxalate metabolic activity at about 15 mM oxalate.

[0185] In certain embodiments, when tested in an in vitro oxalate metabolism assay, the active microorganisms of the present disclosure significantly reduce the concentration of oxalate present in a sample by at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, or at least about 80%.

[0186] In certain embodiments, the active microorganisms of the present disclosure, when administered to a subject, significantly reduce the concentration of oxalate present in a blood, serum, bile, feces, or urine sample by at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, or at least about 80% compared to untreated control subjects or pre-administration levels. The concentration of oxalate in a blood, serum, bile, feces, or urine sample can be measured using liquid chromatography-mass spectrometry (LC-MS). Microbial Support Community

[0187] The microbial consortium of the present disclosure further comprises a support community of microorganisms that improves one or more characteristics of the plurality of active microorganisms. For example, in certain non-limiting embodiments, the support community of microorganisms improves the colonization of the plurality of active microorganisms in the digestive tract. In other embodiments, the support community of microorganisms improves the biomass of the plurality of active microorganisms. In other embodiments, the support community of microorganisms improves the metabolism of a first metabolic substrate by the plurality of active microorganisms. In other embodiments, the support community of microorganisms improves the long-term stability of the plurality of active microorganisms.

[0188] The microbial support community disclosed herein metabolizes one or more metabolites produced by multiple active microorganisms, and the one or more metabolites inhibit the metabolism of the multiple active microorganisms.For example, in certain non-limiting embodiments, the microbial support community metabolizes formate produced by multiple active microorganisms, and the presence of formate inhibits the metabolism of oxalate by multiple active microorganisms.In certain embodiments, the microbial support community of the present disclosure catalyzes the fermentation of polysaccharides into one or more of the group consisting of acetate, acetoin, 2-oxoglutarate, propionate, 1,3-propanediol, succinate, ethanol, lactate, butyrate, 2,3-butanediol, acetone, butanol, formate, H2 and CO2. In certain embodiments, the support community of microorganisms catalyzes the fermentation of amino acids to one or more of the group consisting of acetate, propionate, butanoate, butyrate, isobutyrate, 2-methylbutyrate, isovalerate, isocaproate, 3-phenylpropanoate, phloreate, 3-(1H-indol-3-yl)propanoate, 5-aminopentanoate, H2, H2S, and CO2. In certain embodiments, the supporting community catalyzes the synthesis of one or more of the group consisting of methane from H2 and CO2, methane from formate and H2, acetate from H2 and CO2, acetate from formate and H2, acetate and sulfide from H2, CO2 and sulfate, propionate and CO2 from succinate, succinate from H2 and fumarate; succinate from formate and fumarate, and butyrate, acetate, H2 and CO2 from lactate. In certain embodiments, the support community of microorganisms of the present disclosure catalyzes the deconjugation of conjugated bile acids to produce primary bile acids, the conversion of cholic acid (CA) to 7-oxocholic acid, the conversion of 7-oxocholic acid to 7-beta-cholic acid (7betaCA), the conversion of chenodeoxycholic acid (CDCA) to 7-oxochenodeoxycholic acid, and / or the conversion of 7-oxochenodeoxycholic acid to ursodeoxycholic acid (UDCA). Consortia design

[0189] In certain embodiments, the microbial consortia disclosed herein are designed to meet one or more of the following criteria: (i) capable of eliminating or reducing the level of a first metabolic substrate that causes or contributes to disease in an animal; (ii) capable of metabolizing or converting one or more metabolites produced by metabolism of the first metabolic substrate; (iii) capable of metabolizing one or more nutrients typically found in the human diet; (iv) being able to perform unique and potentially beneficial biological functions in the gastrointestinal (GI) tract (e.g., bile salt hydrolase activity or butyrate production); (v) being able to engraft into various biological niches and physical and metabolic compartments of the GI tract of animals; (vi) the ability to increase biomass by engraftment in the GI tract; (vii) the ability to maintain long-term stability in the GI tract of animals; (viii) capable of increasing the flux of a precursor of a first metabolic substrate into a biochemical pathway that converts said precursor into a metabolite that is not the first metabolic substrate; (ix) the diversity of component microbial species across one or more taxonomic phyla; and (x) Natural prevalence of component microbial species in the GI tract of healthy adults.

[0190] In certain embodiments, the microbial consortium of the present disclosure is designed to include a plurality of active microorganisms capable of metabolizing a first metabolic substrate that causes or contributes to disease in an animal. In certain embodiments, the first metabolic substrate may be selected from, but is not limited to, oxalates and bile acids (e.g., lithocholic acid (LCA), deoxycholic acid (DCA)). In certain embodiments, the microbial consortium is designed to be capable of metabolizing the first metabolic substrate across a range of pH (e.g., pH 4-8) found in the GI tract. In certain embodiments, the microbial consortium is designed to be capable of metabolizing the first metabolic substrate in the presence of a range of first metabolic substrate concentrations, such as those present in different regions of the GI tract.

[0191] In certain embodiments, Consortia is FB-001 (Table 22) or a functional equivalent thereof. In certain embodiments, FB-001 is defined by its function. In certain embodiments, FB-001 is defined by its function as set forth in Tables 23 and / or 24. In certain embodiments, FB-001 is defined by its function as set forth in Tables 23 and 24. In certain embodiments, FB-001 is defined by its function as set forth in Tables 23 or 24. In certain embodiments, FB-001 is defined by its function as set forth in Tables 34, 35, and 36. In certain embodiments, FB-001 is defined by its function as set forth in one or more of Tables 34, 35, and 36. In certain embodiments, FB-001 is defined by its function as set forth in Tables 23, 24, 34, 35, and 36. In certain embodiments, FB-001 is defined by its function as set forth in one or more of Tables 23, 24, 34, 35, and 36. In certain embodiments, FB-001 is defined by its function as set forth in one or more of Tables 23, 24, 34, 35, and 36. In certain embodiments, methods for determining the function of FB-001 are provided in Examples 6 and 7. Preparation method

[0192] The present disclosure also provides methods for preparing and / or producing the microbial consortia described herein. Figures 14-16 show certain methods for preparing and producing the microbial consortia described herein.

[0193] In certain embodiments, the method includes obtaining donor feces and preparing a fecal dilution. In certain embodiments, the fecal dilution is plated on an agar plate. In certain embodiments, the agar plate includes an anaerobic medium. In certain embodiments, the agar plate includes colonies. Characterization and quality analysis of these colonies can be performed. For example, but not by way of limitation, 16s RNA and / or MALDI mass spectrometry could be performed. In certain embodiments, characterized colonies can be further expanded in broth culture. After growth and expansion, the microorganisms can be stored in vials for future use.

[0194] In certain embodiments, the microorganisms can be further expanded in a bioreactor containing cell culture medium. In certain embodiments, the cell culture medium comprises a) soytone, D-cellobiose, yeast extract, dextrose (glucose), maltose monohydrate, magnesium sulfate heptahydrate, calcium chloride dihydrate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, sodium chloride, sodium bicarbonate, volatile fatty acid solution, L-cysteine ​​HCl monohydrate, hemin solution, vitamin solution, or combinations thereof; or b) soytone, D-cellobiose, yeast extract, dextrose (glucose), maltose monohydrate, magnesium sulfate heptahydrate, calcium chloride dihydrate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, sodium chloride, ammonium sulfate, sodium bicarbonate, volatile fatty acid solution, L-cysteine ​​HCl monohydrate, hemin solution, vitamin solution, or combinations thereof. may include.

[0195] In certain embodiments, the cell culture medium is YCFAC. In certain embodiments, the cell culture medium further comprises threonine.

[0196] In certain embodiments, the microorganisms can be expanded in a bioreactor under anaerobic conditions. In certain embodiments, the microorganisms can be expanded in a bioreactor in the presence of a gas overlay. In certain embodiments, the microorganisms can be expanded in a bioreactor in the absence of gas sparging.

[0197] In certain embodiments, the method includes expanding the microorganisms in a mixed culture.

[0198] In certain embodiments, the method comprises: a) Clostridium citroniae, Bacteroides salyersiae, Blautia obeum, Parabacteroides merdae, Parabacteroides distasonis, Anaerostipes hadrus, Lachnospiraceae sp.FBI00033, Eubacterium eligens, Bifidobacterium dentium, Blautia wexlerae, Fusicatenibacter saccharivorans, Bacteroides nordii, Dorea formicigenerans, Dorea longicatena, Bacteroides stercorirosoris, Bifidobacterium longum, Bacteroides kribbi, Lachnospiraceae sp.FBI00071, Bacteroides thetaiotaomicron, Clostridium clostridioforme, Clostridium scindens, Roseburia hominis, Clostridium fessum, Coprococcus comes, Blautia faecis, Hungatella hathewayi, Bacteroides stercoris, Collinsella aerofaciens, Hungatella effluvii, Bifidobacterium adolescentis, Bifidobacterium catenulatum, Lactobacillus rogosae, Bacteroides faecis, Bacteroides finegoldii、Clostridiaceae sp.FBI00191, Ruminococcus faecis, Lachnoclostridium pacaense, Clostridium bolteae, Longicatena caecimuris, Eggerthella lenta, Blautia massiliensis, Bacteroides xylanisolvens, Bacteroides vulgatus, Megasphaera massiliensis, Butyricimonas faecihominis, Eisenbergiella or. b) FBI00001, FBI00002, FBI00010, FBI00013, FBI00029, FBI00032, FBI00033, FBI00034, FBI00043, FBI00044, FBI00048, FBI00050, FBI00051, FBI000 57, FBI00059, FBI00060, FBI00070, FBI00071, FBI00076, FBI00079, FBI00087, FBI00093, FBI00102, FBI00109, FBI00117, FBI00120, FBI00125, FBI001 27, FBI00128, FBI00145, FBI00162, FBI00174, FBI00184, FBI00190, FBI00191, FBI00194, FBI00198, FBI00199, FBI00200, FBI00201, FBI00205, FBI00206, FBI00211, FBI00220, FBI00221, FBI00236, FBI00245, FBI00248, FBI00251, FBI00254, FBI00267, FBI00278, FBI00288, and FBI00290, or functional equivalents thereof. The method includes a step of expanding the microorganisms in the first mixed culture or composition, comprising:

[0199] In certain embodiments, the method comprises: a) Acutalibacter timonensis, Alistipes onderdonkii, Bacteroides uniformis, Eubacterium rectale, Alistipes timonensis, Bacteroides kribbi, Coprococcus eutactus, Bilophila wadsworthia, Bacteroides caccae, Alistipes shahii, Parasutterella excrementihominis, Paraprevotella clara, Sutterella wadsworthensis, Sutterella massiliensis, Porphyromonas asaccharolytica, Ruminococcus bromii, Monoglobus pectinolyticus, Ruminococcaceae sp.FBI00097, Gordonibacter pamelaeae, Bacteroides uniformis, Gordonibacter pamelaeae, Bacteroides fragilis, Phascolarctobacterium faecium, Monoglobus pectinolyticus, Clostridium aldenense, Ruthenibacterium lactatiformans, Bacteroides ovatus, Bifidobacterium bifidum, Anaerotruncus massiliensis, Clostridium aldenense, Sutterella wadsworthensis, Catabacter hongkongensis, Alistipes senegalensis、Ruminococcaceae sp.FBI00233, Alistipes shahii, Dielma fastidiosa, Eubacterium siraeum, Faecalibacterium prausnitzii, Turicibacter sanguinis, Eubacterium rectale, Bacteroides caccae, Methanobrevibacter smithii, Barnesiella intestinihominis, Alistipes onderdonkii, and Methanobrevibacter smithii, or functional equivalents thereof; or. b) FBI00004, FBI00012, FBI00015, FBI00018, FBI00019, FBI00021, FBI00038, FBI00040, FBI00046, FBI00061, FBI00066, FBI0 0075, FBI00077, FBI00080, FBI00081, FBI00085, FBI00092, FBI00097, FBI00099, FBI00112, FBI00132, FBI00137, FBI00140, FB I00149, FBI00151, FBI00176, FBI00189, FBI00197, FBI00208, FBI00212, FBI00224, FBI00226, FBI00229, FBI00233, FBI00235, FBI00237, FBI00243, FBI00244, FBI00258, FBI00260, FBI00263, FBI00270, FBI00273, FBI00277, and FBI00292, or their functional equivalents. expanding the microorganisms in the second mixed culture or composition, comprising:

[0200] In certain embodiments, the method comprises: a) Bifidobacterium adolescentis, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bacteroides thetaiotaomicron, Coprococcus comes, Fusicatenibacter saccharivorans, Eggerthella lenta, Eubacterium eligens, Bacteroides xylanisolvens, Lactobacillus rogosae, Clostridium citoniae, Collinsella aerofaciens, Blautia obeum, Eggerthella lenta, Blautia wexlerae, Lachnoclostridium pacaense, Bacteroides vulgatus, Parabacteroides merdae, Dorea formicigenerans, Ruminococcus faecis, Roseburia hominis, Anaerostipes hadrus, Bifidobacterium adolescentis, Bifidobacterium pseudocatenulatum, Clostridium bolteae, Eisenbergiella tayi, Dorea longicatena, Eggerthella lenta, Bacteroides stercoris, Hungatella hathawayi, and Bacteroides xylanisolvens, or their functional equivalents; or b) FBI00009, FBI00011, FBI00016, FBI00020, FBI00025, FBI00027, FBI00030, FBI00047, FBI00052, FBI00053, FBI00056, FBI00062, FBI00078, FBI00096, FBI00104, FBI00110, FB I00111, FBI00113, FBI00115, FBI00116, FBI00123, FBI00124, FBI00126, FBI00135, FBI00147, FBI00159, FBI00167, FBI00170, FBI00232, FBI00255, and FBI00271, or their functional equivalents. expanding the microorganisms in the third mixed culture or composition, comprising:

[0201] In certain embodiments, the method comprises: a)Alistipes putredinis, Dialister succinatiphilus, Akkermansia muciniphila, Ruminococcus bromii, Dialister invisus, Bacteroides massiliensis, Bilophila wadsworthia, Holdemanella biformis, Parasutterella excrementihominis, Alistipes sp.FBI00180, Bacteroides coprocola, Alistipes sp.FBI00238, Alistipes putredinis, Eubacterium xylanophilum, and Senegalimassilia anaerobia, or a functional equivalent thereof; or b) FBI00022, FBI00049, FBI00068, FBI00069, FBI00152, FBI00165, FBI00171, FBI00175, FBI00177, FBI00180, FBI00182, FBI00238, FBI00269, FBI00274, and FBI00281, or their functional equivalents. expanding the microorganisms in the fourth mixed culture or composition, comprising:

[0202] In certain embodiments, the method includes expanding the microorganism in a monoculture.

[0203] In certain embodiments, the method includes expanding microorganisms in a first monoculture (or a fifth composition) comprising: a) a first O. formigenes strain; or b) FBI00067 or a functional equivalent thereof.

[0204] In certain embodiments, the method includes expanding the microorganisms in a second monoculture (or sixth composition) comprising: a) a second O. formigenes strain; or b) FBI00133 or a functional equivalent thereof.

[0205] In certain embodiments, the method includes expanding the microorganisms in a third monoculture (or seventh composition) comprising: a) a third O. formigenes strain; or b) FBI00289 or a functional equivalent thereof.

[0206] In certain embodiments, the method comprises freeze-drying the cultures and compositions described herein. In certain embodiments, the cultures and compositions comprise a lyoprotectant. In certain embodiments, the lyoprotectant comprises maltodextrin. In certain embodiments, the lyoprotectant comprises inulin. In certain embodiments, the lyoprotectant comprises maltodextrin and inulin. In certain embodiments, the maltodextrin is present at a concentration of about 8%. In certain embodiments, the inulin is present at a concentration of about 0.5%.

[0207] In certain embodiments, the method comprises blending and / or mixing the lyophilized cultures and compositions outlined above. Additional information regarding the strains for each composition can be found in Table 22.

[0208] In certain embodiments, DS1 as set forth in Table 22 is prepared using the method described in FIG. 23. In certain embodiments, DS2 as set forth in Table 22 is prepared using the method described in FIG. 24. In certain embodiments, DS3 as set forth in Table 22 is prepared using the method described in FIG. 25. In certain embodiments, DS4 as set forth in Table 22 is prepared using the method described in FIG. 26. In certain embodiments, DS5-DS7 as set forth in Table 22 (i.e., O. formigenes production) are prepared using the method described in FIG. 22. In certain embodiments, the production of FB-001 includes separate production of each of DS1-DS7 as described in FIGS. 22-26, followed by blending to achieve uniform distribution for each of the DS. In certain embodiments, blending DS1-DS7 is followed by encapsulation for oral administration. Pharmaceutical Compositions

[0209] The present disclosure also provides pharmaceutical compositions that contain an effective amount of the microbial consortium described herein.The composition can be formulated for use in various delivery systems.One or more physiologically acceptable buffers or carriers can also be included in the composition of suitable formulation.Formulations suitable for use in the present disclosure can be found in Remington's Pharmaceutical Sciences, Mack Publishing Company, Philadelphia, Pa., 17th ed., 1985.For a brief review of methods for drug delivery, see, for example, Langer (Science 249:1527-1533, 1990).

[0210] In certain embodiments, the microbial cells of the present disclosure are harvested by microfiltration and centrifugation. In certain embodiments, the microfiltration is performed using a membrane comprising a non-reactive polymer. For example, in certain non-limiting embodiments, the membrane comprises polyvinylidene fluoride, polysulfone, or nitrocellulose. In certain embodiments, the membrane for microfiltration has a pore size of approximately 0.2 to 0.45 μm. In certain embodiments, the cells are harvested using a pore size of approximately 1000 to 30000, 5000 to 30000, 10000 to 30000, 15000 to 30000, 20000 to 30000, 25000 to 30000, 1000 to 25000, 5000 to 25000, 10000 to 25000, 15000 to 25000 , 20,000-25,000, 1000-20,000, 5000-20,000, 10,000-20,000, 15,000-20,000, 1000-15,000, 5000-15,000, 10,000-15,000, 1000-10,000, 5000-10,000, 1000-5,000 g. In certain embodiments, the cells are at approximately 1 x 10 per milliliter. 6 CFU ~ 1 x 10 per milliliter 12 CFU, 1 x 10 per milliliter 7 CFU ~ 1 x 10 per milliliter 12 CFU, 1 x 10 per milliliter 8 CFU ~ 1 x 10 per milliliter 12 CFU, 1 x 10 per milliliter 9 CFU ~ 1 x 10 per milliliter 12 CFU, 1 x 10 per milliliter 10 CFU ~ 1 x 10 per milliliter 12 CFU, 1 x 10 per milliliter 11 CFU ~ 1 x 10 per milliliter 12 CFU, 1 x 10 per milliliter 6 CFU ~ 1 x 10 per milliliter 11 CFU, 1 x 10 per milliliter 7 CFU ~ 1 x 10 per milliliter 11 CFU, 1 x 10 per milliliter 8 CFU ~ 1 x 10 per milliliter11 CFU, 1 x 10 per milliliter 9 CFU ~ 1 x 10 per milliliter 11 CFU, 1 x 10 per milliliter 10 CFU ~ 1 x 10 per milliliter 11 CFU, 1 x 10 per milliliter 6 CFU ~ 1 x 10 per milliliter 10 CFU, 1 x 10 per milliliter 7 CFU ~ 1 x 10 per milliliter 10 CFU, 1 x 10 per milliliter 8 CFU ~ 1 x 10 per milliliter 10 CFU, 1 x 10 per milliliter 9 CFU ~ 1 x 10 per milliliter 10 CFU, 1 x 10 per milliliter 6 CFU ~ 1 x 10 per milliliter 9 CFU, 1 x 10 per milliliter 7 CFU ~ 1 x 10 per milliliter 9 CFU, 1 x 10 per milliliter 8 CFU ~ 1 x 10 per milliliter 9 CFU, 1 x 10 per milliliter 6 CFU ~ 1 x 10 per milliliter 8 CFU, 1 x 10 per milliliter 7 CFU ~ 1 x 10 per milliliter 8 CFU, or 1 x 10 per milliliter 6 CFU ~ 1 x 10 per milliliter 7 Concentrated to CFU.

[0211] In certain embodiments, the microbial cells of the present disclosure are frozen. In certain embodiments, the microbial cells of the present disclosure are mixed with one or more cryoprotectants (CPAs) prior to freezing. In certain embodiments, the ratio of cells to CPA is approximately 25:1, 10:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:10, or 1:25. In certain embodiments, the CPA comprises one or more of glycerol, maltodextrin, sucrose, inulin, trehalose, and alginate. In certain embodiments, the CPA further comprises one or more antioxidants. In certain embodiments, the antioxidant is selected from the list of cysteine, ascorbic acid, and riboflavin.

[0212] In certain embodiments, the microbial cells of the present disclosure are freeze-dried. In certain embodiments, the freeze-dried cells are used to make the oral dose of the present disclosure. In certain embodiments, primary drying is performed at approximately below -20°C. In certain embodiments, primary drying is followed by secondary drying at a higher temperature, for example, above 0°C, above 5°C, or above 10°C. Drugs functionally equivalent and identical to FB-001

[0213] The strains included in FB-001 are described herein by 16S RNA sequence and functional characteristics. Based on this, a Consortia equivalent to FB-001 can be generated by screening multiple identical strains to find equivalent strains with equivalent functions to those that make up FB-001. Thus, identical strains can theoretically have different functions, and functionally identical and equivalent strains can be identified from any fecal collection using the collection method described herein by screening strains using 16S RNA and Biolog as described herein.

[0214] It is important to note that FB-001 was specifically designed to have multiple identical strains in the Consortia. The reason for this is to ensure functionality by having redundancies; however, such redundancies are not required for equivalent functionality if one of the other overlapping strains is included in the final drug product in sufficient viable cell counts to achieve in vivo function in a subject. Thus, a Consortia that is equivalent or identical to FB-001 may contain all overlaps (see Table 22), or alternatively, may contain no overlaps or fewer overlaps per strain, provided that the included strains achieve in vivo function in a subject.

[0215] In an alternative approach to create a Consortia functionally equivalent to FB-001, one skilled in the art could recreate a consortium of supporting microorganisms from healthy fecal donors and supplement the supporting microorganisms with one or more O.formigenes strains. In certain embodiments, the supporting microorganisms will be supplemented with two or more O.formigenes strains, or in particular three O.formigenes strains. The supporting microorganisms may include any number of microorganisms between 10 and 200, provided that such a supporting community supports and promotes the growth, health and engraftment of the O.formigenes strains in the subject. FB-001 was designed to have 148 microorganisms to mimic a complete, healthy microbiome. Thus, an equivalent Consortia may include roughly 148 microorganisms, including the O.formigenes strain. Interestingly, however, older subjects often have a smaller microbiome. Thus, a Consortia functionally equivalent to FB-001 may have many fewer microorganisms (e.g., 30-40, 40-50, 50-60, 60-70, 70-80, 8-90, 90-100, 100-110, 110-120, 120-130, 130-140, or 140-150 microorganisms including O. formigenes strains). Therapeutic Applications

[0216] The present disclosure provides Consortia that can populate one or more niches of the digestive tract, where they can metabolize a first metabolic substrate that causes or contributes to disease in an animal. In certain embodiments, the animal is a human.

[0217] In certain embodiments of the present disclosure, when administered to an animal, the animal is pre-treated with one or more antibiotics prior to administration of the Consortium. In certain embodiments, the one or more antibiotics are selected from ampicillin, enrofloxacin, clarithromycin, and metronidazole. In certain embodiments, the animal is pre-treated with a polyethylene glycol gut preparation procedure.

[0218] In certain embodiments, when administered to an animal, the Consortia significantly reduces the concentration of the first metabolic substrate present in blood, serum, bile, feces, or urine as compared to samples collected pre-treatment from the same animal or from a corresponding control animal that has not received the microbial consortium.

[0219] In certain embodiments, Consortia is used to treat subjects with or at risk of developing a metabolic disease or condition. In certain embodiments, the metabolic disease is primary hyperoxaluria. In certain embodiments, the metabolic disease is secondary hyperoxaluria. In certain embodiments, the metabolic disease is enteric hyperoxaluria. In certain embodiments, the metabolic disease is secondary hyperoxaluria associated with bowel resection surgery or IBD. In certain embodiments, Consortium, when administered to a subject, significantly reduces the concentration of oxalate present in blood, serum, bile, feces or urine samples by at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, or at least about 80% compared to untreated subjects or pre-administration concentrations.

[0220] In certain embodiments, Consortia significantly alters the profile and / or concentration of bile acids present in the animal. For example, in certain non-limiting embodiments, Consortia significantly alters the profile and / or concentration of Tβ-MCA, Tα-MCA, TUDCA, THDCA, TCA, 7β-CA, 7-oxo-CA, TCDCA, Tω-MCA, TDCA, α-MCA, β-MCA, ω-MCA, Muro-CA, d4-CA, CA, TLCA, UDCA, HDCA, CDCA, DCA and LCA in the animal.

[0221] In certain embodiments, the highly complex defined gut microbial communities of the present disclosure can be used to treat animals with cholestatic diseases, such as primary sclerosing cholangitis, primary biliary cholangitis, progressive familial intrahepatic cholestasis, or nonalcoholic steatohepatitis, etc. For example, in certain non-limiting embodiments, the animal can be a mammal, and more particularly a human.

[0222] In certain embodiments, the Consortia can be administered by the intestinal route. For example, in certain non-limiting embodiments, the microbial consortium is administered orally, rectally (e.g., by enema, suppository, or colonoscope), or by oral or nasal tube.

[0223] In certain embodiments, Consortia is administered orally. In certain embodiments, oral administration is by powder. In certain embodiments, oral administration is by slurry. In certain embodiments, oral administration is by pill or capsule.

[0224] In certain embodiments, Consortia can be administered to specific locations along the digestive tract. For example, in certain non-limiting embodiments, microbial consortia can be administered to one or more digestive tract locations, including the mouth, esophagus, stomach, small intestine (duodenum, jejunum, ileum), large intestine (cecum, ascending colon, transverse colon, descending colon), or rectum. In certain embodiments, microbial consortia can be administered to all regions of the digestive tract. Methods for Treating Hyperoxaluria

[0225] In certain embodiments, Consortia is used to treat hyperoxaluria. Hyperoxaluria is a metabolic disorder characterized by a significant increase in urinary oxalate (UOx) excretion (>40mg / 24 hours), which can lead to kidney stone formation and ultimately kidney damage. It is caused by a genetic defect that results in the overproduction of oxalate by the liver (primary) or by a genetic defect that results in the absorption of excess oxalate from the diet (secondary). Secondary hyperoxaluria is further characterized as either dietary, resulting from an over-intake of oxalate or its precursors, or enteric hyperoxaluria (EH). Enteric hyperoxaluria is a complex medical condition characterized by an overabsorption of dietary oxalate, usually caused by fat malabsorption, e.g., after gastric bypass surgery, or by increased intestinal permeability to oxalate due to underlying digestive disease. 24-hour UOx excretion is an established disease biomarker routinely measured in clinical practice to diagnose and manage patients at risk for EH and calcium oxalate kidney stones. Increased UOx increases the risk of kidney stone events, while a 20% or greater decrease would reduce kidney stone incidence by 25% or greater. The increased UOx excretion (>40 mg / 24 hours) that characterizes EH occurs because nonabsorbable fatty acids bind to calcium in the small intestine, making calcium unavailable to precipitate oxalates. As a result, soluble oxalates accumulate in the lumen to relatively high concentrations and can passively diffuse from the colon into the blood for excretion in urine. Calcium oxalate crystals can precipitate within the renal tubules, bind to epithelial cells, and cause obstruction. The attached crystals can be phagocytosed and transcytosed into the renal interstitium, thereby releasing inflammatory mediators that may contribute to oxalate nephropathy and potentially progressive loss of renal function.

[0226] In certain embodiments, the symptoms of hyperoxaluria may vary, but the first clinical manifestation is often the appearance of kidney stones (nephrolithiasis), which can be very painful and debilitating, and may require removal.Oxalate can complex with calcium to form insoluble crystals, so chronically elevated UOx levels are a major risk factor for the development of kidney stones and ultimately kidney damage. Regardless of the frequency of kidney stones, oxalate nephropathy in patients with severe hyperoxaluria can lead to progressive renal function decline, chronic kidney disease (CKD), and eventually end-stage renal disease (ESRD), which can be fatal.

[0227] The prevalence of EH has increased in recent years, affecting more than 250,000 Americans. Of the 250,000 patients with EH in the US in 2019, approximately 60% were the result of RYGB surgery for the treatment of obesity. As the overall prevalence of obesity has increased in recent years, bariatric surgery procedures, particularly RYGB, have emerged as a widely used procedure to treat obesity. Although the RYGB procedure can be advantageous for patients, including increased life expectancy and reduced risk of obesity-related cancer, it can also result in EH within 6 to 24 months of surgery, which can progress to kidney stones and, in severe cases, kidney damage. A 36.4% increase in UOx was identified as a key stone formation risk factor after RYGB in an analysis of seven studies involving 277 patients before or after RYGB. In addition, plasma oxalate and urinary calcium oxalate supersaturation were found to be significantly increased 6 and 12 months after RYGB compared to preoperative levels. Taken together, biomarkers such as urinary and plasma oxalate and calcium oxalate supersaturation are excellent prognostic indicators of EH, kidney stone formation and kidney damage, and reduction of these markers may lead to improved outcome.

[0228] There are currently no approved therapies to reduce UOx excretion in patients with EH. Management or standard treatment options for patients with EH are limited to high fluid intake to increase urine output, correction of underlying GI disease to reduce fat malabsorption, intensive dietary modification to reduce oxalate intake, and the use of calcium salts to bind oxalate in the GI tract. Adherence to these strategies tends to be low, and many patients continue to experience hyperoxaluria with recurrent kidney stones and are at continued risk for significant, irreversible, progressive kidney damage over time.

[0229] In certain embodiments, the Consortia described herein comprises one or more O.formigenes strains and can be administered to a subject for the treatment of enteric hyperoxaluria. In certain embodiments, the Consortia described herein comprises one or more O.formigenes strains and can be administered to a subject for the treatment of hyperoxaluria. In certain embodiments, the Consortia described herein comprises one or more O.formigenes strains and can be administered to a subject for the treatment of primary hyperoxaluria. In certain embodiments, the Consortia described herein comprises one or more O.formigenes strains and can be administered to a subject for the treatment of secondary hyperoxaluria. In certain embodiments, FB-001 can be administered to a subject for the treatment of enteric hyperoxaluria. In certain embodiments, FB-001 can be administered to a subject for the treatment of hyperoxaluria. In certain embodiments, FB-001 can be administered to a subject for the treatment of primary hyperoxaluria. In certain embodiments, FB-001 can be administered to a subject for the treatment of secondary hyperoxaluria. In certain embodiments, the treatment of hyperoxaluria with FB-001 or its functionally equivalent Consortia includes a reduction in intestinal permeability (Figure 19). In certain embodiments, the treatment of hyperoxaluria with FB-001 or its functionally equivalent Consortia includes an increase in the production of SCFAs or equivalent to normal, healthy gut (Figure 20). In certain embodiments, the treatment of hyperoxaluria with FB-001 or its functionally equivalent Consortia includes a reduction in urinary oxalate independent of diet (Figures 20A-20D). In certain embodiments, the treatment of hyperoxaluria with FB-001 or its functionally equivalent Consortia includes oxalate degradation (Figure 21). In certain embodiments, the treatment of hyperoxaluria with FB-001 or its functionally equivalent Consortia includes a reduction in urinary oxalate degradation (Figure 22). In certain embodiments, the treatment of hyperoxaluria with FB-001 or its functionally equivalent Consortia includes a reduction in urinary oxalate degradation (Figure 23). 3In certain embodiments, treatment of hyperoxaluria with FB-001 or its functional equivalent Consortia reduces the rate of oxalate degradation by at least 10 2 In certain embodiments, treatment of hyperoxaluria with FB-001 or its functional equivalent Consortia reduces the rate of oxalate degradation by at least 10 4 In certain embodiments, treatment of hyperoxaluria with FB-001 or its functional equivalent Consortia reduces the rate of oxalate degradation by at least 10 3 In certain embodiments, treatment of hyperoxaluria with FB-001 or its functional equivalent Consortia provides at least 10 1 In certain embodiments, treatment of hyperoxaluria with FB-001 or its functional equivalent Consortia provides at least 10 2 In certain embodiments, treatment of hyperoxaluria with FB-001 or its functional equivalent Consortia is in the range of 10 3 In certain embodiments, treatment of hyperoxaluria with FB-001 or its functional equivalent Consortia provides at least 10 mg / dose / hour of oxalate degradation at a rate of oxalate consumption of at least 10 mg / dose / hour (FIG. 21). -1 Included are oxalate degradation at the rate of oxalate consumption in mg / dose / hr (FIG. 21). Dosage

[0230] In certain embodiments, Consortia is administered as a single dose or multiple doses. In certain embodiments, Consortia is administered once a day for 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, or 1 year. In certain embodiments, Consortia is administered multiple times a day. In certain embodiments, Consortia is administered twice a day, three times a day, four times a day, or five times a day. In certain embodiments, Consortia is administered intermittently. In certain embodiments, Consortia is administered once a week, once a month, or when the subject needs it.

[0231] In certain embodiments, Consortia is administered at a dose effective to allow for engraftment and substrate metabolism. In certain embodiments, Consortia is administered at a dose effective to allow for engraftment and oxalate metabolism. In certain embodiments, Consortia is administered at a dose effective to allow for engraftment and urinary oxalate reduction.

[0232] In certain embodiments, Consortia is administered in a first loading dose, followed by a maintenance dose. In certain embodiments, the first loading dose is administered for 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 days. In certain embodiments, the loading dose is administered for 1-3 days. In certain embodiments, the loading dose is administered for 2-4 days. In certain embodiments, the loading dose is administered for 2-3 days. In certain embodiments, the loading dose is administered for 3-5 days. In certain embodiments, the loading dose is administered for 4-6 days. In certain embodiments, the loading dose is administered for 5-7 days. In certain embodiments, the loading dose is administered for 1 day. In certain embodiments, the loading dose is administered for 3 days. In certain embodiments, the loading dose is administered for 2 days. In certain embodiments, the maintenance dose is administered for 5-10 days after the last loading dose. In certain embodiments, the maintenance dose is administered for 7-12 days after the last loading dose. In certain embodiments, the maintenance dose is administered for 10-14 days after the last loading dose. In certain embodiments, the maintenance dose is administered for 14-21 days after the last loading dose. In certain embodiments, the maintenance dose is administered for 21-28 days after the last loading dose. In certain embodiments, the maintenance dose is administered for 14 days after the last loading dose. In certain embodiments, the maintenance dose is administered for 21 days after the last loading dose. In certain embodiments, the maintenance dose is administered for 28 days after the last loading dose. In certain embodiments, the maintenance dose is administered for about 8 days after the last loading dose. In certain embodiments, the maintenance dose is administered for about 7 days after the last loading dose. In certain embodiments, the maintenance dose is administered for about 6 days after the last loading dose. In certain embodiments, the maintenance dose is administered for about 9 days after the last loading dose. In certain embodiments, the maintenance dose is administered for about 10 days after the last loading dose. In certain embodiments, the loading dose is administered for 2 days and the maintenance dose is administered for 6 days (for a total treatment course of 8 days). In certain embodiments, the loading dose is administered for 2 days and the maintenance dose is administered for 7 days (for a total treatment course of 9 days).In certain embodiments, the loading dose is administered for 2 days and the maintenance dose is administered for 8 days (for a total treatment course of 10 days). In certain embodiments, the loading dose is administered for 9 days and the maintenance dose is administered for 9 days (for a total treatment course of 11 days). In certain embodiments, the loading dose is administered for 2 days and the maintenance dose is administered for 10 days (for a total treatment course of 12 days). In certain embodiments, Consortia is FB-001. In certain embodiments, the loading dose is followed by pretreatment with antibiotics as described in the Combination Therapy section below. In certain embodiments, the loading dose is followed by pretreatment with bowel preparation as described in the Combination Therapy section below. In certain embodiments, the loading dose is followed by pretreatment with antibiotics and bowel preparation as described in the Combination Therapy section below.

[0233] In certain embodiments, FB-001 (i.e., FB-001) is formulated by blending seven lyophilized DSs containing 148 microbial species and filling them into coated enteric capsules. In certain embodiments, the capsules are provided in blister packaging or alternative packaging to allow for zero or low oxygen exposure (e.g., packaging to sustain viability of anaerobic microorganisms). In certain embodiments, each capsule contains 5×10 10 ~5×10 11 In one particular embodiment, each capsule contains in the range of 5×10 viable cells / capsule. 9 ~5×10 10 In one particular embodiment, each capsule contains in the range of 5×10 viable cells / capsule. 11 ~5×10 12 In certain embodiments, FB-001 contains up to 10 viable cells / capsule on days 1 and 2. 12 viable cells, and up to 10 on days 3–10 11 The capsule is orally administered in a single live cell. In certain embodiments, maltodextrin is included as an excipient in the capsule.

[0234] In certain embodiments, FB-001 is comprised of approximately 10-15% O. formigenes. In certain embodiments, FB-001 is comprised of approximately 15-20% O. formigenes. In certain embodiments, FB-001 is comprised of approximately 20-25% O. formigenes. In certain embodiments, FB-001 is comprised of approximately 25-30% O. formigenes. In certain embodiments, FB-001 is comprised of approximately 30-35% O. formigenes. In certain embodiments, FB-001 is comprised of approximately 35-40% O. formigenes. In certain embodiments, FB-001 is comprised of approximately 45-50% O. formigenes. In certain embodiments, three strains of O. formigenes having 16S RNA sequences of SEQ ID NOs: 42, 79 and 146 are provided in approximately equal amounts. In certain embodiments, the three strains of O. formigenes having the 16S RNA sequences of SEQ ID NOs: 42, 79, and 146 are provided in unequal amounts. In certain embodiments, the three strains of O. formigenes having the 16S RNA sequences of SEQ ID NOs: 42, 79, and 146 are provided in similar amounts. In certain embodiments, the three strains of O. formigenes having the 16S RNA sequences of SEQ ID NOs: 42, 79, and 146 are provided in equal amounts.

[0235] In certain embodiments, the total O. formigenes content of each capsule is approximately 25-35% on a relative abundance basis. In certain embodiments, the total O. formigenes content of each capsule is approximately 20%, 21%, 22%, 23%, 24% or 25% on a relative abundance basis. In certain embodiments, the total O. formigenes content of each capsule is approximately 15%, 16%, 17%, 18% or 19% on a relative abundance basis. In certain embodiments, the total O. formigenes content of each capsule is approximately 20%, 21%, 22%, 23%, 24% or 25% on a relative abundance basis. In certain embodiments, the total O. formigenes content of each capsule is approximately 30%, 31%, 32%, 33%, 34% or 35% on a relative abundance basis.

[0236] In certain embodiments, the total O. formigenes content of each capsule is approximately 32% on a relative abundance basis. In certain embodiments, this translates to a total O. formigenes content of 40% on a viable cell count basis. In certain embodiments, for the remaining strains, the relative abundance values ​​ranged from 18% to 0.015%, or three orders of magnitude. In certain embodiments, the distribution is typical of the human microbiome, following a power law distribution, with most species at low relative abundance. In certain embodiments, the absence of detection of a strain should not be interpreted as its absence in the drug substance. In certain embodiments, the 60 detected strains account for 95.932% of the biomarkers detected in FB-001 DP. In certain embodiments, the remaining 88 strains therefore account for 4.068% of the biomarkers. In certain embodiments, the relative abundance profiles are expected to vary between batches, and data will continue to be collected during development to understand the magnitude of variation.

[0237] In one particular embodiment, each capsule of FB-001 contains 5×10 10 ~5×10 11Based on viable cell counting, the relative abundance values ​​for the remaining 145 strains ranged from 18% to 0.015%, with roughly 40% O. formigenes.

[0238] In certain embodiments, dosing includes a 10-day treatment consisting of a loading dose of 10 capsules (1x10^12 viable cells) on days 1 and 2 and a dose of 1 capsule (1x10^11 viable cells) on days 3-10. In certain embodiments, this dosing scheme follows pretreatment with an antibiotic as described herein. In certain embodiments, the antibiotic pretreatment includes pretreatment with 500 mg metronidazole and 500 mg clarithromycin as described herein. In certain embodiments, this dosing scheme follows pretreatment with a bowel preparation as described herein. In certain embodiments, the bowel preparation includes pretreatment with MiraLax. In certain embodiments, this dosing scheme follows pretreatment with an antibiotic as described herein and pretreatment with a bowel preparation as described herein. Combination therapy

[0239] In certain embodiments, Consortia can be administered in combination with other drugs.In certain embodiments, Consortia can be administered with antimicrobial, antifungal, antiviral, antiparasitic, or prebiotics.In certain embodiments, Consortia can be administered after the administration of antimicrobial, antifungal, antiviral, antiparasitic, or prebiotics.In certain embodiments, administration can be sequential or simultaneous over a period of hours or days.

[0240] For example, in certain non-limiting embodiments, the microbial consortium can be administered or pre-administered with one or more antibacterial agents selected from fluoroquinolone antibiotics (ciprofloxacin, levaquin, floxin, tequin, avelox, and norflox); cephalosporin antibiotics (cephalexin, cefuroxime, cefadroxil, cefazolin, cephalothin, cefaclor, cefamandole, cefoxitin, cefprozil, and ceftobiprole); penicillin antibiotics (amoxicillin, ampicillin, penicillin V, dicloxacillin, carbenicillin, vancomycin, and methicillin); tetracycline antibiotics (tetracycline, minocycline, oxytetracycline, and doxycycline); and carbapenem antibiotics (ertapenem, doripenem, imipenem / cilastatin, and meropenem).

[0241] For example, in certain non-limiting embodiments, the microbial consortium may be selected from the group consisting of abacavir, acyclovir, adefovir, amprenavir, atazanavir, cidofovir, darunavir, delavirdine, didanosine, docosanol, efavirenz, elvitegravir, emtricitabine, enfuvirtide, etravirine, famciclovir, foscamet, fomivirsen, ganciclovir, indinavir, idoxuridine, lamivudine, lopinavir, serovar 100, serovar 100, serovar 100, serovar 100, and serovar 100. The therapeutic agent may be administered with one or more antiviral agents selected from ribavirin, maraviroc, MK-2048, nelfinavir, nevirapine, penciclovir, raltegravir, rilpivirine, ritonavir, saquinavir, stavudine, tenofovir, trifluridine, valacyclovir, valganciclovir, vidarabine, ibasitabine, amantadine, oseltamivir, rimantidine, tipranavir, zalcitabine, zanamivir, and zidovudine.

[0242] In certain embodiments, the microbial consortium is treated with an antifungal agent selected from the group consisting of miconazole, ketoconazole, clotrimazole, econazole, omoconazole, bifonazole, butoconazole, fenticonazole, isoconazole, oxiconazole, sertaconazole, sulconazole, and tioconazole; triazole antifungals, such as fluconazole, itraconazole, isavuconazole, ravuconazole, posaconazole, voriconazole, terconazole, and albaconazole; It may be administered with one or more antifungal agents selected from thiazole antifungals, such as abafungin; allylamine antifungals, such as terbinafine, naftifine, and butenafine; and echinocandin antifungals, such as anidulafungin, caspofungin, and micafungin; poligodial; benzoic acid; ciclopirox; tolnaftate; undecylenic acid; flucytosine or 5-fluorocytosine; griseofulvin; and haloprogin.

[0243] In certain embodiments, the microbial consortium may be administered with one or more anti-inflammatory and / or immunosuppressive agents selected from cyclophosphamide, mycophenolate mofetil, corticosteroids, mesalazine, mesalamine, sulfasalazine, sulfasalazine derivatives, cyclosporine A, mercaptopurine, azathioprine, prednisone, methotrexate, antihistamines, glucocorticoids, epinephrine, theophylline, sodium cromoglycate, anti-leukotrienes, anticholinergics, monoclonal anti-IgE, immunomodulatory peptides, immunomodulatory small molecules, immunomodulatory cytokines, immunomodulatory antibodies, and vaccines.

[0244] In certain embodiments, Consortia may be administered with one or more prebiotics selected from, but not limited to, amino acids, biotin, fructooligosaccharides, galactooligosaccharides, inulin, lactose, mannanoligosaccharides, oligofructose-enriched inulin, oligofructose, oligodextrose, tagatose, trans-galactooligosaccharides, and xylooligosaccharides.

[0245] In certain embodiments, Consortia described herein is administered in combination with NOV-001 (Novome). In certain embodiments, Consortia is administered prior to administration of NOV-001 (Novome). In certain embodiments, Consortia is administered following administration of NOV-001 (Novome). In certain embodiments, Consortia is administered concurrently with administration of NOV-001 (Novome). In certain embodiments, the Consortia administered in combination with NOV-001 (Novome) is FB-001.

[0246] In certain embodiments, Consortia is administered in combination with SYNB8802 (Synlogic). In certain embodiments, Consortia is administered prior to administration of SYNB8802 (Synlogic). In certain embodiments, Consortia is administered following administration of SYNB8802 (Synlogic). In certain embodiments, Consortia is administered concurrently with administration of SYNB8802 (Synlogic). In certain embodiments, the Consortia administered in combination with SYNB8802 (Synlogic) is FB-001.

[0247] In certain embodiments, Consortia is administered in combination with OX-1 (Oxidien). In certain embodiments, Consortia is administered before administration of OX-1 (Oxidien). In certain embodiments, Consortia is administered after administration of OX-1 (Oxidien). In certain embodiments, Consortia is administered in parallel with administration of OX-1 (Oxidien). In certain embodiments, the Consortia administered in combination with OX-1 (Oxidien) is FB-001.

[0248] In certain embodiments, Consortia is administered in combination with lumasiran (Alnylam). In certain embodiments, Consortia is administered prior to administration of lumasiran (Alnylam). In certain embodiments, Consortia is administered following administration of lumasiran (Alnylam). In certain embodiments, Consortia is administered concurrently with administration of lumasiran (Alnylam). In certain embodiments, the Consortia administered in combination with lumasiran (Alnylam) is FB-001.

[0249] In certain embodiments, Consortia is administered in combination with Nedosiran (Dicerna). In certain embodiments, Consortia is administered prior to administration of Nedosiran (Dicerna). In certain embodiments, Consortia is administered after administration of Nedosiran (Dicerna). In certain embodiments, Consortia is administered concurrently with administration of Nedosiran (Dicerna). In certain embodiments, the Consortia administered in combination with Nedosiran (Dicerna) is FB-001.

[0250] In certain embodiments, Consortia is administered in combination with BBP-711 (Cantero / Bridge Bio). In certain embodiments, Consortia is administered prior to administration of BBP-711 (Cantero / Bridge Bio). In certain embodiments, Consortia is administered following administration of BBP-711 (Cantero / Bridge Bio). In certain embodiments, Consortia is administered concurrently with administration of BBP-711 (Cantero / Bridge Bio). In certain embodiments, the Consortia administered in combination with BBP-711 (Cantero / Bridge Bio) is FB-001.

[0251] In certain embodiments, Consortia is administered in combination with CNK-336 (Chinook). In certain embodiments, Consortia is administered before administration of CNK-336 (Chinook). In certain embodiments, Consortia is administered after administration of CNK-336 (Chinook). In certain embodiments, Consortia is administered in parallel with administration of CNK-336 (Chinook). In certain embodiments, the Consortia administered in combination with CNK-336 (Chinook) is FB-001.

[0252] In certain embodiments, Consortia is administered in combination with PBGENE-PH1 (Precision Bio). In certain embodiments, Consortia is administered prior to administration of PBGENE-PH1 (Precision Bio). In certain embodiments, Consortia is administered following administration of PBGENE-PH1 (Precision Bio). In certain embodiments, Consortia is administered concurrently with administration of PBGENE-PH1 (Precision Bio). In certain embodiments, the Consortia administered in combination with PBGENE-PH1 (Precision Bio) is FB-001.

[0253] In certain embodiments, Consortia is administered in combination with a low oxalate diet. In certain embodiments, Consortia is administered in combination with a high hydration diet. In certain embodiments, Consortia is administered in combination with a calcium supplement. In certain embodiments, Consortia is administered in combination with a low oxalate diet and a calcium supplement. In certain embodiments, Consortia is FB-001, and FB-001 is administered in combination with a low oxalate diet and a calcium supplement, or a low oxalate diet and a calcium supplement. In certain embodiments, the calcium supplement comprises a diet that has sufficient calcium without further supplementation.

[0254] In certain embodiments, Consortia is administered in combination with 1) one of NOV-001, 2) OX-1, (Oxidien), lumasiran (Alnylam), nedosiran (Dicerna), BBP-711 (Cantero / Bridge Bio), CNK-336 (Chinook), and PBGENE-PH1 (Precision Bio), and 2) a low oxalate diet. In certain embodiments, Consortia is administered in combination with 1) one of NOV-001, 2) OX-1, (Oxidien), lumasiran (Alnylam), nedosiran (Dicerna), BBP-711 (Cantero / Bridge Bio), CNK-336 (Chinook), and PBGENE-PH1 (Precision Bio), and 2) a high calcium diet (including but not limited to calcium supplements). In certain embodiments, Consortia is administered in combination with 1) one of NOV-001, 2) OX-1, (Oxidien), lumasiran (Alnylam), nedosiran (Dicerna), BBP-711 (Cantero / Bridge Bio), CNK-336 (Chinook), and PBGENE-PH1 (Precision Bio), 2) a low oxalate diet, and 3) a high calcium diet (including but not limited to calcium supplements). In certain embodiments, FB-001 is administered in combination with 1) one of NOV-001, 2) OX-1, (Oxidien), lumasiran (Alnylam), nedosiran (Dicerna), BBP-711 (Cantero / Bridge Bio), CNK-336 (Chinook), and PBGENE-PH1 (Precision Bio), and 2) a low oxalate diet. In certain embodiments, FB-001 is administered in combination with 1) one of NOV-001, 2) OX-1, (Oxidien), lumasiran (Alnylam), nedosiran (Dicerna), BBP-711 (Cantero / Bridge Bio), CNK-336 (Chinook), and PBGENE-PH1 (Precision Bio), and 2) a high calcium diet (including but not limited to calcium supplements).In certain embodiments, FB-001 is administered in combination with 1) one of NOV-001, 2) OX-1, (Oxidien), lumasiran (Alnylam), nedosiran (Dicerna), BBP-711 (Cantero / Bridge Bio), CNK-336 (Chinook), and PBGENE-PH1 (Precision Bio), 2) a low oxalate diet, and 3) a high calcium diet (including but not limited to calcium supplements). In certain embodiments within this paragraph, "in combination" refers to concurrent, prior to, or subsequent to administration of Consortia. In certain embodiments within this paragraph, "in combination" refers to concurrent, prior to, or subsequent to administration of FB-001.

[0255] In certain embodiments, the Consortia combination treatment includes antibiotic pretreatment. In certain embodiments, the antibiotic pretreatment includes 2, 3, 4, 5, 6, or 7 days of pretreatment. In certain embodiments, the pretreatment is 4, 5, or 6 days. In certain embodiments, the pretreatment is 5 days. In certain embodiments, the antibiotic pretreatment includes 500 mg of metronidazole. In certain embodiments, the antibiotic pretreatment includes 500 mg of clarithromycin. In certain embodiments, the antibiotic pretreatment includes 500 mg of metronidazole and 500 mg of clarithromycin. In certain embodiments, the antibiotic pretreatment consists of 500 mg of metronidazole and 500 mg of clarithromycin. In certain embodiments, the antibiotic dose may be adjusted based on the subject's weight. In certain embodiments, 500 mg of metronidazole and 500 mg of clarithromycin are administered every 12 hours (Q12h). In certain embodiments, there is a one day interval between the last dose of antibiotic and administration of Consortia. In certain embodiments, there is a two day interval between the last dose of antibiotic and administration of Consortia. In certain embodiments, metronidazole and / or clarithromycin may be used in place of one or more different antibiotics having a similar or substantially similar mechanism of action (e.g., type of antibacterial agent). In certain embodiments, metronidazole and / or clarithromycin may be used in place of one or more different antibiotics having a similar or substantially similar mechanism of action (e.g., type of antibacterial agent) if the subject has a hypersensitivity or allergy to metronidazole and / or clarithromycin, respectively. In certain embodiments, Consortia is FB-001. In certain embodiments, Consortia is FB-001 and the pretreatment is 500 mg metronidazole and 500 mg clarithromycin administered as a pretreatment Q12h for 5 days.In certain embodiments, Consortia is FB-001 and the pretreatment is 500 mg metronidazole and 500 mg clarithromycin administered as a pretreatment Q12h for 5 days with a 1 day interval between administration of the last dose of antibiotic and administration of the first dose of FB-001. In certain embodiments, Consortia is FB-001 and the pretreatment is 500 mg metronidazole and 500 mg clarithromycin administered as a pretreatment Q12h for 5 days with no interval between administration of the last dose of antibiotic and administration of the first dose of FB-001.

[0256] In certain embodiments, the bowel preparation (e.g., MiraLax) is administered in the late afternoon or evening after the last dose of antibiotic, which is administered in the morning of the same day. In certain embodiments, the bowel preparation (e.g., MiraLax) is administered in the late afternoon or evening after the last dose of 500 mg metronidazole and 500 mg clarithromycin, which is administered in the morning of the same day. In certain embodiments, MiraLax is administered at least 8 hours after the last dose of 500 mg metronidazole and 500 mg clarithromycin. In certain embodiments, metronidazole and / or clarithromycin may be substituted for one or more different antibiotics with similar or substantially similar mechanisms of action (e.g., type of antibacterial agent). In certain embodiments, the bowel preparation is MiraLax. In certain embodiments, 238 g of MiraLax is administered. In certain embodiments, MiraLax is mixed with a flavored hydration beverage, such as Gatorade, Gatorade Unsweetened, or similar trademarks. In certain embodiments, MiraLax is mixed with approximately 2 L of the flavored hydration beverage. In certain embodiments, MiraLax is mixed with approximately 1.5-2 L of the flavored hydration beverage. In certain embodiments, MiraLax is mixed with approximately 1.9 L of the flavored hydration beverage. In certain embodiments, the diluted MiraLax is consumed by the subject at approximately 8 oz every 10-20 minutes. In certain embodiments, the diluted MiraLax is consumed by the subject at approximately 8 oz every 10-15 minutes. In certain embodiments, the diluted MiraLax is completely consumed by the subject within 90-150 minutes. In certain embodiments, the diluted MiraLax is completely consumed by the subject within 100-140 minutes. In certain embodiments, the diluted MiraLax is completely consumed by the subject within 100-130 minutes. In certain embodiments, the diluted MiraLax is completely consumed by the subject within 100-120 minutes.In certain embodiments, the diluted MiraLax is completely consumed by the subject within 120 minutes. In certain embodiments, the Consortia is FB-001. In certain embodiments, the MiraLax pretreatment comprises 238 g of MiraLax mixed (i.e., diluted) into approximately 1.9 L of a flavored rehydration beverage (e.g., zero sugar Gatorade) that is completely consumed by the subject within approximately 120 minutes (e.g., 8 oz every 10-20 minutes) at least 8 hours after the last dose of 500 mg metronidazole and 500 mg clarithromycin, and the Consortia is administered the day after the MiraLax administration. In one particular embodiment, the Consortia is FB-001, the MiraLax pretreatment comprises 238 g of MiraLax mixed (i.e., diluted) into approximately 1.9 L of a flavored rehydration beverage (e.g., zero sugar Gatorade) that is consumed completely by the subject within approximately 120 minutes (e.g., 8 oz every 10-20 minutes) at least 8 hours after the last dose of 500 mg metronidazole and 500 mg clarithromycin, and FB-001 is administered the day after MiraLax administration. kit

[0257] The subject matter of the present disclosure provides a kit for treating hyperoxaluria, enteric hyperoxaluria, primary hyperoxaluria, and secondary hyperoxaluria in a subject. In certain embodiments, the kit comprises an effective amount of the Consortia of the present disclosure or a pharmaceutical composition comprising the same. In certain embodiments, the kit comprises an effective amount of FB-001 or a pharmaceutical composition comprising the same. In certain embodiments, the kit comprises an effective amount of Consortia functionally equivalent to FB-001 or a pharmaceutical composition comprising the same. In certain embodiments, the kit comprises an effective amount of Consortia functionally identical to FB-001 or a pharmaceutical composition comprising the same. In certain embodiments, the kit comprises an effective amount of Consortia substantially similar to FB-001 or a pharmaceutical composition comprising the same. In certain embodiments, the kit comprises an effective amount of Consortia similar to FB-001 or a pharmaceutical composition comprising the same. In certain embodiments, the kit includes a sterile container, which may be a box, an ampoule, a bottle, a vial, a tube, a bag, a pouch, a blister pack, or other suitable containers known in the art. Such containers may be made of plastic, glass, laminated paper, metal foil, or other materials suitable for holding pharmaceuticals. In certain non-limiting embodiments, the kit includes an anaerobic container for holding the Consortia described herein. In certain non-limiting embodiments, the kit includes a blister pack for holding the Consortia described herein in the absence of oxygen or in the presence of limited amounts of oxygen. In certain non-limiting embodiments, the kit includes a blister pack with a desiccant for holding the Consortia described herein in the absence of oxygen or in the presence of limited amounts of oxygen. In certain non-limiting embodiments, the kit includes a bottle with a desiccant for holding the Consortia described herein in the absence of oxygen or in the presence of limited amounts of oxygen.

[0258] In certain embodiments, the kit comprises instructions for administering Consortia as described herein. In certain embodiments, the instructions comprise instructions for administering a loading and maintenance dose.

[0259] In certain embodiments, the kit comprises storage instructions. In certain embodiments, the storage instructions are for storage at approximately -20°C. In certain embodiments, the storage instructions are for storage below -5°C. In certain embodiments, the storage instructions are for storage at approximately -15 to -20°C, -10 to -20°C, -10 to -15°C, -5 to -10°C, 0 to -5°C, below 0°C, or 0 to -20°C. In certain embodiments, the storage instructions are for storage below approximately 4°C. In certain embodiments, the storage instructions are for storage at room temperature.

[0260] In certain embodiments, the kit includes instructions for maintaining the Consortia in oxygen-free or low-oxygen conditions.

[0261] In certain embodiments, the kit includes instructions for a low oxalate and / or high calcium diet, hi certain embodiments, the kit includes instructions for maintaining hydration.

[0262] In certain embodiments, the kit contains instructions for the subject to maintain a cessation of all antibiotics during treatment with Consortia.

[0263] In certain embodiments, the kit comprises FB-001 and instructions for administering FB-001. Exemplary embodiments

[0264] In certain non-limiting embodiments, the present disclosure relates to a composition comprising a microbial consortium comprising at least one oxalate metabolizing microbial strain, wherein at least one strain expresses an enzyme selected from formyl-CoA transferase, oxalate-formate exchanger, and oxalyl-CoA decarboxylase.

[0265] In certain embodiments of the compositions disclosed herein, at least one oxalate metabolizing microbial strain is from the genus Oxalobacter.

[0266] In certain embodiments of the compositions disclosed herein, the composition comprises at least three oxalate metabolizing microbial strains, wherein the at least three oxalate metabolizing microbial strains are different strains of the same species.

[0267] In certain embodiments of the compositions disclosed herein, the composition comprises at least three oxalate metabolizing microbial strains, wherein the at least three oxalate metabolizing microbial strains are different strains of different species.

[0268] In certain embodiments of the compositions disclosed herein, the species is Oxalobacter formigenes (O. formigenes), and optionally, the number of oxalate metabolizing microbial strains is three or more.

[0269] In certain embodiments of the compositions disclosed herein, a) at least one strain is a low pH tolerant strain; b) at least one strain is a high oxalate resistant strain; and / or c) At least one of the strains is a high growth rate strain.

[0270] In certain non-limiting embodiments, the present disclosure provides a composition comprising at least two Oxalobacter formigenes (O. formigenes) strains, each of the strains exhibiting one or more of the following functions: a) Low pH tolerant strains; b) high oxalate resistant strains; and / or c) High growth rate strain The present invention relates to a composition comprising:

[0271] In certain non-limiting embodiments, the present disclosure relates to a composition comprising at least three Oxalobacter formigenes (O. formigenes) strains, where a) at least one strain is a low pH tolerant strain; b) at least one strain is a high oxalate tolerant strain; and c) at least one strain is a high growth rate strain.

[0272] In certain embodiments of the compositions disclosed herein, the low pH tolerant strain is capable of metabolizing oxalate at a pH between about 4 and about 6.

[0273] In certain embodiments of the compositions disclosed herein, the low pH tolerant strain is capable of metabolizing oxalate at a pH of about 5.

[0274] In certain embodiments of the compositions disclosed herein, the high oxalate tolerant strain is capable of metabolizing oxalate at concentrations between about 5 mM and about 30 mM.

[0275] In certain embodiments of the compositions disclosed herein, the high oxalate tolerant strain is capable of metabolizing oxalate at a concentration of about 15 mM.

[0276] In certain embodiments of the compositions disclosed herein, each strain comprises a 16s RNA nucleotide sequence that is (a) at least about 80% identical to the nucleotide sequence set forth in SEQ ID NO:42, SEQ ID NO:79, or SEQ ID NO:146, (b) at least about 90% identical to the nucleotide sequence set forth in SEQ ID NO:42, SEQ ID NO:79, or SEQ ID NO:146, or (c) at least about 96% identical to the nucleotide sequence set forth in SEQ ID NO:42, SEQ ID NO:79, or SEQ ID NO:146.

[0277] In certain embodiments of the compositions disclosed herein, each strain comprises a 16s RNA nucleotide sequence that is at least about 97% identical or 98.5% identical to the nucleotide sequence set forth in SEQ ID NO:42, SEQ ID NO:79, or SEQ ID NO:146.

[0278] In certain embodiments of the compositions disclosed herein, each strain comprises a 16s RNA nucleotide sequence identical to the nucleotide sequence set forth in SEQ ID NO:42, SEQ ID NO:79, or SEQ ID NO:146.

[0279] In certain embodiments of the compositions disclosed herein, the composition further comprises one or more microorganisms that metabolize formate.

[0280] In certain embodiments of the compositions disclosed herein, the composition further comprises one or more microorganisms that catalyze the fermentation of polysaccharides.

[0281] In certain embodiments of the compositions disclosed herein, the composition further comprises one or more microorganisms that catalyze the fermentation of an amino acid.

[0282] In certain embodiments of the compositions disclosed herein, the composition further comprises a microorganism that catalyzes the synthesis of at least one molecule selected from the group consisting of methane, acetate, sulfide, propionate, and succinate.

[0283] In certain embodiments of the compositions disclosed herein, the compositions further comprise a microorganism that catalyzes a) deconjugation of conjugated bile acids to produce primary bile acids, b) conversion of cholic acid (CA) to 7-oxocholic acid, c) conversion of 7-oxocholic acid to 7-beta-cholic acid (7betaCA), d) conversion of chenodeoxycholic acid (CDCA) to 7-oxochenodeoxycholic acid, and / or e) conversion of 7-oxochenodeoxycholic acid to ursodeoxycholic acid (UDCA).

[0284] In certain embodiments of the compositions disclosed herein, the composition is selected from the group consisting of: a) Consortia I or a functional equivalent thereof; b) Consortia II or a functional equivalent thereof; c) Consortia III or a functional equivalent thereof; d) Consortia IV or a functional equivalent thereof; e) Consortia V or a functional equivalent thereof; f) Consortia VI or a functional equivalent thereof; g) Consortia VII or a functional equivalent thereof; h) Consortia VIII or a functional equivalent thereof; i) Consortia IX or a functional equivalent thereof; j) Consortia X or a functional equivalent thereof; k) Consortia XI or a functional equivalent thereof; l) Consortia XII or a functional equivalent thereof; m) Consortia XIII or a functional equivalent thereof; n) Consortia XIV or a functional equivalent thereof; o) Consortia XV or a functional equivalent thereof; p) Consortia XVI or a functional equivalent thereof; q) Consortia XVII or its functional equivalent; r) Consortia XVIII or its functional equivalent; or s) Consortia XIX or its functional equivalent.

[0285] In certain embodiments of the compositions disclosed herein, the composition comprises Clostridium citoniae, Bacteroides salyersiae, Blautia obeum, Parabacteroides merdae, Parabacteroides distasonis, Anaerostipes hadrus, Lachnospiraceae sp. FBI00033, Eubacterium eligens, Bifidobacterium dentium, Blautia wexlerae, Fusicatenibacter saccharivorans, Bacteroides nordii, Dorea formicigenerans, Dorea longicatena, Bacteroides stercorirosoris, Bifidobacterium longum, Bacteroides kribbi, Lachnospiraceae sp. FBI00071, Bacteroides thetaiotaomicron, Clostridium clostridioforme, Clostridium scindens, Roseburia hominis, Clostridium fessum, Coprococcus comes, Blautia faecis, Hungatella hathewayi, Bacteroides stercoris, Collinsella aerofaciens, Hungatella effluvii, Bifidobacterium adolescentis, Bifidobacterium catenulatum, Lactobacillus rogosae, Bacteroides faecis, Bacteroides finegoldii, Clostridiaceae sp.FBI00191, Ruminococcus faecis, Lachnoclostridium pacaense, Clostridium bolteae, Longicatena caecimuris, Eggerthella lenta, Blautia massiliensis, Bacteroides xylanisolvens, Bacteroides vulgatus, Megasphaera massiliensis, Butyricimonas faecihominis, Eisenbergiella tayi, Acidaminococcus intestini, Emergencia timonensis, Bifidobacterium pseudocatenulatum, Eubacterium hallii, Anaerofustis stercorihominis, Eubacterium ventriosum, Blautia hydrogenotrophica, Lachnospiraceae sp. FBI00290, or a functionally equivalent microbial consortium.

[0286] In certain embodiments of the compositions disclosed herein, the composition comprises FBI00001, FBI00002, FBI00010, FBI00013, FBI00029, FBI00032, FBI00033, FBI00034, FBI00043, FBI00044, FBI00048, FBI00050, FBI00051, FBI00057, FBI00059, FBI00060, FBI00070, FBI00071, FBI00076, FBI00079, FBI00087, FBI00093, FBI00102, FBI00109, FBI00117, FBI00120, FBI00132, FBI00134, FBI00136, FBI00138, FBI00138, FBI00139, FBI00140, FBI00141, FBI00142, FBI00143, FBI00144, FBI00145, FBI00146, FBI00147, FBI00148, FBI00149, FBI00150, FBI00151, FBI00152, FBI00153, FBI00154, FBI00155, FBI00156, FBI00157, FBI00158, FBI00159, FBI00160, FBI00161, FBI00162, FBI00163, FBI00164, FBI00165, FBI00166, FBI00167, FBI00168, FBI00169, FBI0 FBI00236, FBI00245, FBI00248, FBI00251, FBI00254, FBI00267, FBI00278, FBI00288, FBI00290, or a functional equivalent thereof.

[0287] In certain embodiments of the compositions disclosed herein, each strain comprises (a) SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:83, SEQ ID NO:89, SEQ ID NO: (b) at least about 80% identical to the nucleotide sequence set forth in SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, Column number 21, SEQ ID NO:22, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:83, SEQ ID NO:89, SEQ ID NO:94, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, or (c) is at least about 90% identical to the nucleotide sequence set forth in SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38,The nucleotide sequence of the 16s RNA is at least about 96% identical to the nucleotide sequence set forth in SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:83, SEQ ID NO:89, SEQ ID NO:94, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:136, SEQ ID NO:143, SEQ ID NO:145, or SEQ ID NO:147.

[0288] In certain embodiments of the compositions disclosed herein, each strain is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:8 3, SEQ ID NO:89, SEQ ID NO:94, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:136, SEQ ID NO:143, SEQ ID NO:145, or SEQ ID NO:147.

[0289] In certain embodiments of the compositions disclosed herein, each strain is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:74, SEQ ID NO:76 , SEQ ID NO:77, SEQ ID NO:83, SEQ ID NO:89, SEQ ID NO:94, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:136, SEQ ID NO:143, SEQ ID NO:145, or SEQ ID NO:147.

[0290] Acutalibacter timonensis, Alistipes, is the most common strain of the strain of the strain onderdonkii、Bacteroides uniformis、Eubacterium rectale、Alistipes timonensis、Bacteroides kribbi、Coprococcus eutactus、Bilophila wadsworthia、Bacteroides caccae、Alistipes shahii、Parasutterella excrementihominis、Paraprevotella clara、Sutterella wadsworthensis、Sutterella massiliensis、Porphyromonas asaccharolytica、Ruminococcus bromii、Monoglobus pectinilyticus、Ruminococcaceae sp.FBI00097、Gordonibacter pamelaeae、Bacteroids uniformis、Gordonibacter pamelaeae、Bacteroides fragilis、Phascolarctobacterium faecium、Monoglobus pectinilyticus、Clostridium aldenense、Ruthenibacterium lactatiformans、Bacteroides ovatus、Bifidobacterium bifidum、Anaerotruncus massiliensis、Clostridium aldenense、Sutterella wadsworthensis、Catabacter hongkongensis、Alistipes senegalensis、Ruminococcaceae sp.FBI00233, Alistipes shahii, Dielma fastidiosa, Eubacterium siraeum, Faecalibacterium prausnitzii, Turicibacter sanguinis, Eubacterium rectale, Bacteroides caccae, Methanobrevibacter smithii, Barnesiella intestinihominis, Alistipes onderdonkii, Methanobrevibacter smithii, or a functional equivalent thereof.

[0291] In certain embodiments of the compositions disclosed herein, the composition is selected from the group consisting of FBI00004, FBI00012, FBI00015, FBI00018, FBI00019, FBI00021, FBI00038, FBI00040, FBI00046, FBI00061, FBI00066, FBI00075, FBI00077, FBI00080, FBI00081, FBI00085, FBI00092, FBI00097, FBI00099, FBI00112, FBI00132, FBI00134, FBI00136, FBI00138 ... 7, FBI00140, FBI00149, FBI00151, FBI00176, FBI00189, FBI00197, FBI00208, FBI00212, FBI00224, FBI00226, FBI00229, FBI00233, FBI00235, FBI00237, FBI00243, FBI00244, FBI00258, FBI00260, FBI00263, FBI00270, FBI00273, FBI00277, FBI00292, or a functional equivalent thereof.

[0292] In certain embodiments of the compositions disclosed herein, each strain comprises (a) SEQ ID NO:3, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:27, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:66, SEQ ID NO:78, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:96, SEQ ID NO:101, SEQ ID NO:105, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO: 117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, or SEQ ID NO:148; (b) at least about 80% identical to the nucleotide sequence set forth in SEQ ID NO:3, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:27, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, and at least the nucleotide sequence set forth in SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:66, SEQ ID NO:78, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:96, SEQ ID NO:101, SEQ ID NO:105, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, or SEQ ID NO:148. or (c) SEQ ID NO:3, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:27, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:66, SEQ ID NO:78, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:96, SEQ ID NO:101, SEQ ID NO:105, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119,The nucleotide sequence of the 16s RNA is at least about 96% identical to the nucleotide sequence set forth in SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, or SEQ ID NO:148.

[0293] In certain embodiments of the compositions disclosed herein, each strain comprises a 16s RNA nucleotide sequence that is at least about 97% identical or 98.5% identical to the nucleotide sequence set forth in SEQ ID NO:3, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:27, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:66, SEQ ID NO:78, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:96, SEQ ID NO:101, SEQ ID NO:105, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, or SEQ ID NO:148.

[0294] In certain embodiments of the compositions disclosed herein, each strain comprises a 16s RNA nucleotide sequence identical to the nucleotide sequence set forth in SEQ ID NO:3, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:27, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:66, SEQ ID NO:78, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:96, SEQ ID NO:101, SEQ ID NO:105, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, or SEQ ID NO:148.

[0295] In certain embodiments of the compositions disclosed herein, the composition is selected from the group consisting of Bifidobacterium adolescentis, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bacteroides thetaiotaomicron, Coprococcus comes, Fusicatenibacter saccharivorans, Eggerthella lenta, Eubacterium eligens, Bacteroides xylanisolvens, Lactobacillus rogosae, Clostridium citroniae, Collinsella aerofaciens, Blautia obeum, Eggerthella lenta, Blautia wexlerae, Lachnoclostridium pacaense, Bacteroides vulgatus, Parabacteroides merdae, Dorea formicigenerans, Ruminococcus faecis, Roseburia hominis, Anaerostipes hadrus, Bifidobacterium adolescentis, Bifidobacterium pseudocatenulatum, Clostridium bolteae, Eisenbergiella tayi, Dorea longicatena, Eggerthella lenta, Bacteroides stercoris, Hungatella hathewayi, Bacteroides xylanisolvens, or functional equivalents thereof.

[0296] In certain embodiments of the compositions disclosed herein, the composition comprises any of the following: FBI00009, FBI00011, FBI00016, FBI00020, FBI00025, FBI00027, FBI00030, FBI00047, FBI00052, FBI00053, FBI00056, FBI00062, FBI00078, FBI00096, FBI0010 4, FBI00110, FBI00111, FBI00113, FBI00115, FBI00116, FBI00123, FBI00124, FBI00126, FBI00135, FBI00147, FBI00159, FBI00167, FBI00170, FBI00232, FBI00255, FBI00271, or functional equivalents thereof.

[0297] In certain embodiments of the compositions disclosed herein, each strain is selected from the group consisting of: (a) at least about 80% identical to the nucleotide sequence set forth in SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:10, SEQ ID NO:13, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:28, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:40, SEQ ID NO:50, SEQ ID NO:58, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:88, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:120, SEQ ID NO:132, or SEQ ID NO:139; (b) at least about 80% identical to the nucleotide sequence set forth in SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:10, SEQ ID NO:13, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:28, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:40, SEQ ID NO:50, SEQ ID NO:58, SEQ ID NO:62, SEQ ID NO:64, or (c) a 16s RNA nucleotide sequence that is at least about 90% identical to the nucleotide sequence set forth in SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:88, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:120, SEQ ID NO:132, or SEQ ID NO:139; or (b) a 16s RNA nucleotide sequence that is at least about 96% identical to the nucleotide sequence set forth in SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:10, SEQ ID NO:13, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:28, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:40, SEQ ID NO:50, SEQ ID NO:58, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:88, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:120, SEQ ID NO:132, or SEQ ID NO:139.

[0298] In certain embodiments of the compositions disclosed herein, each strain comprises a 16s RNA nucleotide sequence that is at least about 97% identical or 98.5% identical to the nucleotide sequence set forth in SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:10, SEQ ID NO:13, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:28, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:40, SEQ ID NO:50, SEQ ID NO:58, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:88, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:120, SEQ ID NO:132, or SEQ ID NO:139.

[0299] In certain embodiments of the compositions disclosed herein, each strain comprises a 16s RNA nucleotide sequence identical to the nucleotide sequence set forth in SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:10, SEQ ID NO:13, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:28, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:40, SEQ ID NO:50, SEQ ID NO:58, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:88, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:120, SEQ ID NO:132, or SEQ ID NO:139.

[0300] In certain embodiments of the compositions disclosed herein, the composition further comprises a fifth composition comprising Alistipes putredinis, Dialister succinatiphilus, Akkermansia muciniphila, Ruminococcus bromii, Dialister invisus, Bacteroides massiliensis, Bilophila wadsworthia, Holdemanella biformis, Parasutterella excrementihominis, Alistipes sp. FBI00180, Bacteroides coprocola, Alistipes sp. FBI00238, Alistipes putredinis, Eubacterium xylanophilum, Senegalimassilia anaerobia, or a functional equivalent thereof.

[0301] In certain embodiments of the compositions disclosed herein, the composition further comprises FBI00022, FBI00049, FBI00068, FBI00069, FBI00152, FBI00165, FBI00171, FBI00175, FBI00177, FBI00180, FBI00182, FBI00238, FBI00269, FBI00274, FBI00281, or a functional equivalent thereof.

[0302] In certain embodiments of the compositions disclosed herein, each strain is selected from the group consisting of: (a) a nucleotide sequence that is at least about 80% identical to a nucleotide sequence set forth in SEQ ID NO:15, SEQ ID NO:30, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:87, SEQ ID NO:90, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:125, SEQ ID NO:137, SEQ ID NO:141, or SEQ ID NO:144; (b) a nucleotide sequence that is at least about 80% identical to a nucleotide sequence set forth in SEQ ID NO:15, SEQ ID NO:30, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:87, SEQ ID NO:90, SEQ ID NO:93, SEQ ID NO:95, or (c) a 16s RNA nucleotide sequence that is at least about 90% identical to the nucleotide sequence set forth in SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:125, SEQ ID NO:137, SEQ ID NO:141, or SEQ ID NO:144; or (d) a 16s RNA nucleotide sequence that is at least about 96% identical to the nucleotide sequence set forth in SEQ ID NO:15, SEQ ID NO:30, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:87, SEQ ID NO:90, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:125, SEQ ID NO:137, SEQ ID NO:141, or SEQ ID NO:144.

[0303] In certain embodiments of the compositions disclosed herein, each strain comprises a 16s RNA nucleotide sequence that is at least about 97% identical or 98.5% identical to the nucleotide sequence set forth in SEQ ID NO:15, SEQ ID NO:30, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:87, SEQ ID NO:90, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:125, SEQ ID NO:137, SEQ ID NO:141, or SEQ ID NO:144.

[0304] In certain embodiments of the compositions disclosed herein, each strain comprises a 16s RNA nucleotide sequence identical to the nucleotide sequence set forth in SEQ ID NO:15, SEQ ID NO:30, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:87, SEQ ID NO:90, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:125, SEQ ID NO:137, SEQ ID NO:141, or SEQ ID NO:144.

[0305] In certain non-limiting embodiments, the present disclosure relates to a microbial consortium comprising a microbial strain listed in Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, Table 10, Table 11, Table 12, Table 13, Table 14, Table 15, Table 16, Table 17, Table 18, Table 19, or a functional equivalent thereof.

[0306] In certain non-limiting embodiments, the present disclosure relates to a microbial consortium comprising a microbial strain listed in Table 22, or a functional equivalent thereof.

[0307] In certain embodiments of the microbial consortia disclosed herein, each strain comprises a 16s RNA nucleotide sequence that is (a) at least about 80% identical to a nucleotide sequence set forth in SEQ ID NOs:1-148, (b) at least about 90% identical to a nucleotide sequence set forth in SEQ ID NOs:1-148, or (c) at least about 96% identical to a nucleotide sequence set forth in SEQ ID NOs:1-148.

[0308] In certain embodiments of the microbial consortia disclosed herein, each strain comprises a 16s RNA nucleotide sequence that is at least about 97% identical to, or 98.5% to, the nucleotide sequence set forth in SEQ ID NOs:1-148.

[0309] In certain embodiments of the microbial consortia disclosed herein, each strain comprises a 16s RNA nucleotide sequence identical to a nucleotide sequence set forth in SEQ ID NOs:1-148.

[0310] In certain non-limiting embodiments, the present disclosure relates to a composition comprising the microbial consortium disclosed herein.

[0311] In certain embodiments of the compositions disclosed herein, the composition is a pharmaceutical composition.

[0312] In certain embodiments of the compositions disclosed herein, the composition comprises about 5×10 10 ~Approx. 5×10 11 Contains living cells.

[0313] In certain embodiments of the compositions disclosed herein, the composition comprises about 5×10 9 ~Approx. 5×10 10 Contains living cells.

[0314] In certain embodiments of the compositions disclosed herein, the composition comprises about 5×10 11 ~Approx. 5×10 12 Contains living cells.

[0315] In certain embodiments of the compositions disclosed herein, the composition comprises up to about 5×10 12 Contains living cells.

[0316] In certain embodiments of the compositions disclosed herein, the composition comprises about 10% to about 50% oxalate metabolizing microbial strains.

[0317] In certain embodiments of the compositions disclosed herein, the composition comprises about 10% to about 50% O. formigenes strains on a viable cell count basis.

[0318] In certain embodiments of the compositions disclosed herein, the composition comprises about 20% O. formigenes strains on a viable cell count basis.

[0319] In certain embodiments of the compositions disclosed herein, the composition comprises about 30% O. formigenes strains on a viable cell count basis.

[0320] In certain embodiments of the compositions disclosed herein, the composition comprises about 40% O. formigenes strains on a viable cell count basis.

[0321] In certain non-limiting embodiments, the present disclosure relates to a method for producing the compositions or microbial consortia disclosed herein. In certain embodiments of the methods for producing disclosed herein, the method comprises: a) Clostridium citroniae, Bacteroides salyersiae, Blautia obeum, Parabacteroides merdae, Parabacteroides distasonis, Anaerostipes hadrus, Lachnospiraceae sp.FBI00033, Eubacterium eligens, Bifidobacterium dentium, Blautia wexlerae, Fusicatenibacter saccharivorans, Bacteroides nordii, Dorea formicigenerans, Dorea longicatena, Bacteroides stercorirosoris, Bifidobacterium longum, Bacteroides kribbi, Lachnospiraceae sp.FBI00071, Bacteroides thetaiotaomicron, Clostridium clostridioforme, Clostridium scindens, Roseburia hominis, Clostridium fessum, Coprococcus comes, Blautia faecis, Hungatella hathewayi, Bacteroides stercoris, Collinsella aerofaciens, Hungatella effluvii, Bifidobacterium adolescentis, Bifidobacterium catenulatum, Lactobacillus rogosae, Bacteroides faecis, Bacteroides finegoldii、Clostridiaceae sp.A first composition comprising FBI00191, Ruminococcus faecis, Lachnoclostridium pacaense, Clostridium bolteae, Longicatena caecimuris, Eggerthella lenta, Blautia massiliensis, Bacteroides xylanisolvens, Bacteroides vulgatus, Megasphaera massiliensis, Butyricimonas faecihominis, Eisenbergiella tayi, Acidaminococcus intestini, Emergencia timonensis, Bifidobacterium pseudocatenulatum, Eubacterium hallii, Anaerofustis stercorihominis, Eubacterium ventriosum, Blautia hydrogenotrophica, and Lachnospiraceae sp. FBI00290, or a functional equivalent thereof;. b) Acutalibacter timonensis, Alistipes onderdonkii, Bacteroides uniformis, Eubacterium rectale, Alistipes timonensis, Bacteroides kribbi, Coprococcus eutactus, Bilophila wadsworthia, Bacteroides caccae, Alistipes shahii, Parasutterella excrementihominis, Paraprevotella clara, Sutterella wadsworthensis, Sutterella massiliensis, Porphyromonas asaccharolytica, Ruminococcus bromii, Monoglobus pectinolyticus, Ruminococcaceae sp.FBI00097, Gordonibacter pamelaeae, Bacteroides uniformis, Gordonibacter pamelaeae, Bacteroides fragilis, Phascolarctobacterium faecium, Monoglobus pectinolyticus, Clostridium aldenense, Ruthenibacterium lactatiformans, Bacteroides ovatus, Bifidobacterium bifidum, Anaerotruncus massiliensis, Clostridium aldenense, Sutterella wadsworthensis, Catabacter hongkongensis, Alistipes senegalensis、Ruminococcaceae sp.a second composition comprising FBI00233, Alistipes shahii, Dielma fastidiosa, Eubacterium siraeum, Faecalibacterium prausnitzii, Turicibacter sanguinis, Eubacterium rectale, Bacteroides caccae, Methanobrevibacter smithii, Barnesiella intestinihominis, Alistipes onderdonkii, and Methanobrevibacter smithii, or functional equivalents thereof; c) a third composition comprising Bifidobacterium adolescentis, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bacteroides thetaiotaomicron, Coprococcus comes, Fusicatenibacter saccharivorans, Eggerthella lenta, Eubacterium eligens, Bacteroides xylanisolvens, Lactobacillus rogosae, Clostridium citoniae, Collinsella aerofaciens, Blautia obeum, Eggerthella lenta, Blautia wexlerae, Lachnoclostridium pacaense, Bacteroides vulgatus, Parabacteroides merdae, Dorea formicigenerans, Ruminococcus faecis, Roseburia hominis, Anaerostipes hadrus, Bifidobacterium adolescentis, Bifidobacterium pseudocatenulatum, Clostridium bolteae, Eisenbergiella tayi, Dorea longicatena, Eggerthella lenta, Bacteroides stercoris, Hungatella hathawayi, and Bacteroides xylanisolvens, or functional equivalents thereof; d) a fourth composition comprising Alistipes putredinis, Dialister succinatiphilus, Akkermansia muciniphila, Ruminococcus bromii, Dialister invisus, Bacteroides massiliensis, Bilophila wadsworthia, Holdemanella biformis, Parasutterella excrementihominis, Alistipes sp. FBI00180, Bacteroides coprocola, Alistipes sp. FBI00238, Alistipes putredinis, Eubacterium xylanophilum, and Senegalimassilia anaerobia, or a functional equivalent thereof; e) a fifth composition comprising the first O. formigenes strain; f) a sixth composition comprising a second O. formigenes strain; and / or g) A seventh composition comprising a third O. formigenes strain. and blending.

[0322] In certain embodiments of the methods of manufacture disclosed herein, the method comprises: a) FBI00001, FBI00002, FBI00010, FBI00013, FBI00029, FBI00032, FBI00033, FBI00034, FBI00043, FBI00044, FBI00048, FBI00050, FBI00051, FBI00057, FBI00059, FBI00060, FBI00070, FBI00071, FBI00076, FBI00079, FBI00087, FBI00093, FBI00102, FBI00109, FBI00117, FBI00120, FBI00125, FBI00127, FB a first composition comprising FBI00128, FBI00145, FBI00162, FBI00174, FBI00184, FBI00190, FBI00191, FBI00194, FBI00198, FBI00199, FBI00200, FBI00201, FBI00205, FBI00206, FBI00211, FBI00220, FBI00221, FBI00236, FBI00245, FBI00248, FBI00251, FBI00254, FBI00267, FBI00278, FBI00288, and FBI00290, or a functional equivalent thereof; b) FBI00004, FBI00012, FBI00015, FBI00018, FBI00019, FBI00021, FBI00038, FBI00040, FBI00046, FBI00061, FBI00066, FBI0007 5, FBI00077, FBI00080, FBI00081, FBI00085, FBI00092, FBI00097, FBI00099, FBI00112, FBI00132, FBI00137, FBI00140, FBI0014 9, FBI00151, FBI00176, FBI00189, FBI00197, FBI00208, FBI00212, FBI00224, FBI00226, FBI00229, FBI00233, FBI00235, FBI00237, FBI00243, FBI00244, FBI00258, FBI00260, FBI00263, FBI00270, FBI00273, FBI00277, and FBI00292, or a functional equivalent thereof; c) FBI00009, FBI00011, FBI00016, FBI00020, FBI00025, FBI00027, FBI00030, FBI00047, FB I00052, FBI00053, FBI00056, FBI00062, FBI00078, FBI00096, FBI00104, FBI00110, FBI0011 1, FBI00113, FBI00115, FBI00116, FBI00123, FBI00124, FBI00126, FBI00135, FBI00147, FBI00159, FBI00167, FBI00170, FBI00232, FBI00255, and FBI00271, or functional equivalents thereof; d) a fourth composition comprising FBI00022, FBI00049, FBI00068, FBI00069, FBI00152, FBI00165, FBI00171, FBI00175, FBI00177, FBI00180, FBI00182, FBI00238, FBI00269, FBI00274, and FBI00281, or a functional equivalent thereof; e) a fifth composition comprising FBI00067 or a functional equivalent thereof; f) a sixth composition comprising FBI00133 or a functional equivalent thereof; and / or g) A seventh composition comprising FBI00289 or a functional equivalent thereof. and blending.

[0323] In certain embodiments of the production methods disclosed herein, each strain comprises a 16s RNA nucleotide sequence that is (a) at least about 80% identical to a nucleotide sequence set forth in SEQ ID NOs:1-148, (b) at least about 90% identical to a nucleotide sequence set forth in SEQ ID NOs:1-148, or (c) at least about 96% identical to a nucleotide sequence set forth in SEQ ID NOs:1-148.

[0324] In certain embodiments of the production methods disclosed herein, each strain comprises a 16s RNA nucleotide sequence that is at least about 97% identical or 98.5% identical to the nucleotide sequence set forth in SEQ ID NOs:1-148.

[0325] In certain embodiments of the production methods disclosed herein, each strain comprises a 16s RNA nucleotide sequence identical to the nucleotide sequence set forth in SEQ ID NOs:1-148.

[0326] In certain embodiments of the methods of production disclosed herein, the fourth composition is obtained by growing a microorganism in the presence of threonine.

[0327] In certain embodiments of the methods of manufacture disclosed herein, each composition comprises a lyoprotectant.

[0328] In certain embodiments of the manufacturing methods disclosed herein, each composition comprises maltodextrin, inulin, or a combination thereof.

[0329] In certain embodiments of the methods of manufacture disclosed herein, the maltodextrin is at a concentration of about 8%.

[0330] In certain embodiments of the manufacturing methods disclosed herein, the inulin is at a concentration of about 0.5%.

[0331] In certain embodiments of the manufacturing methods disclosed herein, each composition is lyophilized separately.

[0332] In certain embodiments of the methods of production disclosed herein, the functional equivalent is based on the characteristics set forth in Table 24.

[0333] In certain embodiments of the methods of production disclosed herein, the functional equivalent is based on the characteristics set forth in Table 34.

[0334] In certain embodiments of the methods of production disclosed herein, the functional equivalent is based on the characteristics set forth in Table 35.

[0335] In certain embodiments of the methods of production disclosed herein, the functional equivalent is based on the characteristics set forth in Table 36.

[0336] In certain embodiments of the methods of manufacture disclosed herein, the functional equivalents are based on the characteristics set forth in Tables 34-36.

[0337] In certain embodiments of the production methods disclosed herein, the methods include obtaining and blending microorganisms that contain genes that regulate oxalate degradation, oxalate resistance, formate metabolism, macronutrient metabolism, microbial metabolite production, syntrophic activity, and / or mucin degradation.

[0338] In certain embodiments of the manufacturing methods disclosed herein, the methods include obtaining and blending microorganisms that are known to prevent disease and / or are commonly found in the healthy human gut.

[0339] In certain embodiments of the production methods disclosed herein, the methods include obtaining and blending microorganisms that utilize a carbon source listed in Table 35.

[0340] In certain embodiments of the production methods disclosed herein, each strain can optionally utilize a subset of the carbon sources listed in Table 35.

[0341] In certain embodiments of the manufacturing methods disclosed herein, each composition is prepared using an inoculation density adjustment.

[0342] In certain embodiments of the manufacturing methods disclosed herein, each composition is or has been cultured in the presence of a gas overlay.

[0343] In certain embodiments of the manufacturing methods disclosed herein, each composition is or has been cultured in the absence of gas sparging.

[0344] In certain non-limiting embodiments, the present disclosure relates to compositions prepared by the methods of manufacture disclosed herein.

[0345] In certain non-limiting embodiments, the present disclosure relates to a method of treating hyperoxaluria in a subject in need thereof, comprising administering an effective amount of a composition or microbial consortium disclosed herein.

[0346] In certain non-limiting embodiments, the present disclosure relates to a method of reducing the risk of developing hyperoxaluria in a subject in need thereof, comprising administering an effective amount of a composition or microbial consortium disclosed herein.

[0347] In certain non-limiting embodiments, the present disclosure relates to a method of reducing urinary oxalate in a subject in need thereof, comprising administering an effective amount of a composition or microbial consortium disclosed herein.

[0348] In certain embodiments of the methods disclosed herein, the hyperoxaluria is primary hyperoxaluria, secondary hyperoxaluria, or enteric oxaluria.

[0349] In certain embodiments of the methods disclosed herein, the secondary hyperoxaluria is associated with bowel resection surgery.

[0350] In certain embodiments of the methods disclosed herein, the hyperoxaluria is enteric hyperoxaluria.

[0351] In certain embodiments of the methods disclosed herein, the methods further comprise administering at least one antibacterial agent, antiviral agent, antifungal agent, anti-inflammatory agent, immunosuppressant agent, prebiotic, or a combination thereof.

[0352] In certain embodiments of the methods disclosed herein, the methods further include administering NOV-001, SYNB8802, OX-1, lumasiran, nedosiran, BBP-711, CNK-336, PBGENE-PH1, or a combination thereof.

[0353] In certain embodiments of the methods disclosed herein, the methods further comprise administering a low oxalate diet, a high hydration diet, a calcium supplement, or a combination thereof.

[0354] In certain embodiments of the methods disclosed herein, the composition or microbial consortium is administered orally.

[0355] In certain non-limiting embodiments, the present disclosure relates to a method of treating hyperoxaluria in a subject in need thereof, comprising administering a first dose of a composition or microbial consortium disclosed herein.

[0356] In certain non-limiting embodiments, the present disclosure relates to a method of reducing the risk of developing hyperoxaluria in a subject in need thereof, comprising administering a first dose of a composition or microbial consortium disclosed herein.

[0357] In certain non-limiting embodiments, the present disclosure relates to a method of reducing urinary oxalate in a subject in need thereof, comprising administering a first dose of a composition or microbial consortium disclosed herein.

[0358] In certain embodiments of the methods disclosed herein, the hyperoxaluria is primary hyperoxaluria, secondary hyperoxaluria, or enteric hyperoxaluria.

[0359] In certain embodiments of the methods disclosed herein, the secondary hyperoxaluria is associated with bowel resection surgery.

[0360] In certain embodiments of the methods disclosed herein, the hyperoxaluria is enteric hyperoxaluria.

[0361] In certain embodiments of the methods disclosed herein, the method further comprises the step of administering an antibiotic treatment.

[0362] In certain embodiments of the methods disclosed herein, the antibiotic treatment is administered for about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, or about 7 days.

[0363] In certain embodiments of the methods disclosed herein, the antibiotic is metronidazole, clarithromycin, or a combination thereof.

[0364] In certain embodiments of the methods disclosed herein, antibiotic treatment is completed one day prior to administration of the first dose.

[0365] In certain embodiments of the methods disclosed herein, antibiotic treatment is completed two days prior to administering the first dose.

[0366] In certain embodiments of the methods disclosed herein, the method further comprises administering a treatment that is a bowel preparation treatment.

[0367] In certain embodiments of the methods disclosed herein, the treatment that is an intestinal preparation treatment is administered to the subject after the antibiotic treatment.

[0368] In certain embodiments of the methods disclosed herein, the treatment that is an intestinal preparation treatment is administered before the first dose.

[0369] In certain embodiments of the methods disclosed herein, the first dose comprises an effective amount of the composition or microbial consortium.

[0370] In certain embodiments of the methods disclosed herein, the first dose is about 10 12Contains living cells.

[0371] In certain embodiments of the methods disclosed herein, the first dose is administered for about 1 day.

[0372] In certain embodiments of the methods disclosed herein, the first dose is administered for about two days.

[0373] In certain embodiments of the methods disclosed herein, the methods further comprise administering a second dose of the composition or microbial consortium disclosed herein.

[0374] In certain embodiments of the methods disclosed herein, the second dose comprises an effective amount of the composition or microbial consortium.

[0375] In certain embodiments of the methods disclosed herein, the second dose is about 10 11 Contains living cells.

[0376] In certain embodiments of the methods disclosed herein, the second dose is administered up to about 8 days.

[0377] In certain embodiments of the methods disclosed herein, the second dose is administered up to about 10 days.

[0378] In certain embodiments of the methods disclosed herein, the first dose is administered orally.

[0379] In certain embodiments of the methods disclosed herein, the second dose is administered orally.

[0380] In certain non-limiting embodiments, the present disclosure relates to kits comprising the compositions or microbial consortia disclosed herein.

[0381] In certain embodiments of the kits disclosed herein, the kit comprises a container comprising a desiccant.

[0382] In certain embodiments of the kits disclosed herein, the container comprises anaerobic conditions.

[0383] In certain embodiments of the kits disclosed herein, the container is a blister.

[0384] In certain embodiments of the kits disclosed herein, the kit further comprises written instructions for administering the composition or microbial consortium.

[0385] In certain non-limiting embodiments, the present disclosure relates to a method of culturing a microbial strain from the genus Akkermansia, comprising contacting the strain with N-acetylgalactosamine (GalNAc).

[0386] In certain embodiments of the culturing methods disclosed herein, the strain is Akkermansia muciniphilia.

[0387] In certain non-limiting embodiments, the present disclosure relates to a microbial consortium comprising the functional traits set forth in Table 23.

[0388] In certain non-limiting embodiments, the present disclosure relates to a microbial consortium comprising the functional traits set forth in Table 24.

[0389] In certain non-limiting embodiments, the present disclosure relates to a microbial consortium comprising the functional traits set forth in Table 34.

[0390] In certain non-limiting embodiments, the present disclosure relates to a microbial consortium comprising the functional traits set forth in Table 35.

[0391] In certain non-limiting embodiments, the present disclosure relates to a microbial consortium comprising the functional traits set forth in Table 36.

[0392] In certain non-limiting embodiments, the present disclosure relates to a microbial consortium comprising FB-001 or a functional equivalent thereof.

[0393] In certain non-limiting embodiments, the present disclosure relates to any of the methods or compositions described herein. EXAMPLES

[0394] Example 1 Design of Consortia Microbial consortia of two or more microbial strains have been previously generated, but limitations existed that hindered manufacturing and clinical efficacy. Specifically, manufacturing limitations have hindered the design and generation of large consortia that can colonize the gastrointestinal tract and establish functional microbiota systems.

[0395] Isolation of Donor-Derived Microbial Strains. Microbial strains were isolated and identified using the methods described in PCT / US2021 / 021790.

[0396] Consortia Generation. Using microbial strains identified using the isolation and identification methods described in PCT / US2021 / 021790, over 30 large consortia were generated and examined for their functional ability to metabolize oxalate, absence of phages, acceptable endotoxin levels, and their manufacturability in multi-strain drug substances. The reason for the large number of experimental large consortia was that it was unclear what combination of microbial strains would be optimal given the above considerations. Furthermore, the optimal combination of microbial strains could not be predicted by an algorithm and required wet lab work to determine efficacy and manufacturability.

[0397] Nineteen exemplary consortia are provided in Tables 1-19.

[0398] Pharmaceuticals containing each of the above consortia were tested for their ability to metabolize oxalate using in vitro and / or in vivo assays.

[0399] In an exemplary experiment, an in vitro study was performed using germ-free mice to determine whether diet and existing gut microbiota have an effect on the efficacy of Consortia in reducing oxalate in vivo. Germ-free mice were divided into three groups: 1) diet is refined, high-sugar diet; 2) diet is complex, grain-based diet; and 3) diet is complex, grain-based diet, and mice were colonized with human FMT. Mice from groups 1-3 were then fed one of Consortia I-VIII. The refined, high-sugar diet (also called the Ox36 diet) consisted of 316.22 g / kg sucrose, 280 g / kg corn starch, 200 g / kg casein, 50 g / kg corn oil, 35 g / kg inulin, 35 g / kg pectin, 25 g / kg cellulose, 16.23 g / kg sodium chloride, 13.37 g / kg mineral oil (Ca-P deficient), 11.4 g / kg potassium dihydrogen phosphate, 10 g / kg vitamin mix (Teklad), 3.72 g / kg sodium oxalate, 3 g / kg DL-methionine, 1.05 g / kg calcium chloride, and 0.01 g / kg ethoxyquin (antioxidant). At the time of formulation, the Ox36 diet contained 0.372% sodium oxalate, 1.88% NaCl, 2.5% cellulose, 3.5% inulin, and 3.5% pectin, and the nutrient breakdown of the diet was 58.3% carbohydrate, 17.7% protein, and 5.2% fat (by weight). A complex, grain-based diet was made using PMI Laboratory Autoclavable Rodent Diet (Envigo Cat. No. 5010) supplemented with sodium oxalate and sodium chloride (final product consisted of 970.82 g / Kg of PMI Laboratory Autoclavable Rodent Diet, 21.5 g / Kg of sodium oxalate, and 7.68 g / Kg of sodium chloride), consisting of 22.7% protein, 40.3% carbohydrate, and 5% fat by weight.

[0400] In these experiments, germ-free C57Bl / 6 mice were fed either a refined, sugar-rich diet or a complex, grain-based diet to induce hyperoxaluria. One week later, one of Consortia I-VIII was introduced to the mice by oral gavage. Mice were then sampled to determine microbiome composition and urinary oxalate levels. Specifically, mice were started on diet on day -7, mice were gavaged on day 0, fecal samples were collected on day 7, food intake was measured, and mice were sacrificed on day 14 to collect urine, feces, and plasma samples, and, when possible, cecal images, as well as kidney / liver specimens and / or images. The negative control for these experiments was gavage-feeding of PBS rather than Consortia.

[0401] Oxalate and creatinine were measured by LC-MS / MS from urine samples obtained on the 14th day.

[0402] Representative data from mice fed a complex, grain-based diet and force-fed Consortia are provided in Tables 20 and 21.

[0403] [Table 20]

[0404] [Table 21]

[0405] Moreover, it was surprising to find that the ability of Consortia to reduce urinary oxalate was diet independent. Representative data from mice fed either a complex grain-based diet or a refined high-sugar diet and force-fed Consortia VI (Figure 1A) or VIII (Figure 1B) show that the ability of Consortia to reduce urinary oxalate was diet independent.

[0406] An additional question that remained unclear was whether the pre-existing microbiota in the gastrointestinal tract would affect the efficacy of Consortia. Therefore, the experiments described above were repeated in germ-free mice colonized with human FMT prior to the initiation of an oxalate diet (either a refined, sugary diet or a complex, grain-based diet). As shown in Figure 1C, the pre-existing microbiota did not affect the efficacy of Consortia (in this example, Consortia VII). The ability of Consortia to exert an active effect on reducing urinary oxalate levels regardless of the pre-existing microbiota was unexpected, since the literature suggested that in order for microbiome products to colonize and function in the gastrointestinal tract, it was necessary to use antibiotics to eliminate the pre-existing microbiota.

[0407] Although Table 20 shows that Consortia V was the most effective against oxalate metabolism and degradation (i.e., Consortia V had the lowest concentration of urinary oxalate), further investigation and modification of Consortia was necessary to design a product for the treatment of diseases, particularly diseases that cause or are caused by a reduced or inability to effectively metabolize and degrade oxalate in the gastrointestinal tract. Therefore, modifications of Consortia V were made to determine which microbiota provide functional benefits, including but not limited to consortia growth, oxalate metabolism and degradation, consortia engraftment, and consortia survival, and which microbiota are not required or are detrimental to patients receiving the consortia as a treatment for a disease, or to the function of the consortia as a whole (including but not limited to consortia growth, oxalate metabolism and degradation, consortia engraftment, and consortia survival). Examples of such designed and investigated consortia are Consortia IX-XVI.

[0408] Of the Consortia IX–XVI designed and tested, Consortia IX was selected as the lead for clinical development. Key changes made when modifying the consortia for the treatment of diseases, particularly diseases that cause or are caused by a reduced or inability to effectively metabolize and break down oxalate in the gastrointestinal tract, include the removal of a Citrobacter freundii strain because it was found experimentally to be a facultative anaerobe (see, e.g., removal of strains between Consortia XIII and XV, and between Consortia XXIV, XIII, and XII), replacement of one Bacteroides kribbi species with a different Bacteroides kribbi species cluster (see, e.g., replacement of strains between Consortia XV and XVI), replacement of one Blautia faecis species with a different Blautia faecis species (see, e.g., replacement of strains between Consortia XV and XVI), strains that were determined to be redundant strains based on whole genome sequencing clusters (see, e.g., removal of strains between Consortia XVII and XVI), and the addition of one Bifidobacterium to improve growth in culture. replacement of one Bifidobacterium adolescentis with another Bifidobacterium adolescentis to improve growth in culture (see, for example, strain replacement between Consortia X and XII); replacement of one Bifidobacterium pseudocatenulatum with another Bifidobacterium pseudocatenulatum to improve growth in culture (see, for example, strain replacement between Consortia X and XII); replacement of one Bacteroides xylanisolvens with another Bacteroides xylanisolvens to improve growth in culture (see, for example, strain replacement between Consortia X and XII); replacement of one Clostridium citroniae with another Clostridium citroniae to improve growth in culture (see, for example, strain replacement between Consortia X and XII).replacement of one Blautia faecis with another to identify Blautia strains that could grow sufficiently to create a master cell bank (see, for example, strain replacement between Consortia X and XII); removal of Holdemanella biformis to eliminate phage risk because phages were not detected in co-culture but were detected using bioinformatics methods (see, for example, strain replacement between Consortia X and XII); and removal of Faecalibacterium prasnitzii to eliminate phage risk because phages were not detected in co-culture but were detected using bioinformatics methods (see, for example, strain replacement between Consortia X and XII). Example 2 Oxalobacter formigenes microbiome

[0409] Oxalobacter formigenes (O. formigenes) is a microbiota essential for oxalate degradation and metabolism, and is included in Consortia I-XIX. However, as shown in Tables 1-19 above, certain Consortia have O. formigenes listed three times in each of the Consortia. This is because there are multiple strains of O. formigenes, as well as because experiments have shown that the different strains identified have different physiological functions that directly affect colonization and function in the gastrointestinal tract. The three O. formigenes strains selected for Consortia I-XIX include 1) one strain with low pH tolerance, 2) one strain with high oxalate tolerance, and 3) one strain with a high growth rate.

[0410] While any set of O. formigenes strains that meet criteria 1-3 above can be used in a consortium designed to increase oxalate metabolism and degradation, the strains used in Consortia I-XIX contain 16S RNA sequences of SEQ ID NO:42, SEQ ID NO:79 and SEQ ID NO:146. Example 3 Pharmaceutical Design and Manufacturing

[0411] As shown in Example 1, the Consortia described herein were designed to be a complex community of anaerobic microbiota that can live and function in the gastrointestinal tract. However, previous methods known to those skilled in the art were unable to produce such large consortia. Therefore, new manufacturing methods were required to grow the microbiota in separate groups (i.e., drug substances) to form the final drug product.

[0412] Traditionally, enterobacterial preparations (LBPs) are produced one strain at a time (i.e., single strain production). Single strain production requires fermentation scale-up of each single strain to produce an individual drug substance (each "DS"), followed by lyophilization. Thus, multiple DSs of individual lyophilized strains are then blended into a mixture and filled into capsules or other suitable packaging / filling to produce the final drug product ("DP"). While this works well for small consortia, it is not feasible to grow 100+ strains separately, produce 100+ DSs, and then blend the 100+ DSs into a stable DP. In addition to stability limitations, current technology would require a year or more to produce a single DP. Thus, conventional production using current technology was not an option for a DP containing 100+ strains, preferably 145+ strains as provided for Consortia IX.

[0413] In designing and modifying Consortia as described in Examples 1 and 2, a manufacturing method was developed that can produce a consortia of 145+ strains, including more than 90 species and four or more or six taxonomic phyla found in the human gastrointestinal microbiome. Further, a method was developed and modified for Consortia IX, which includes approximately 99 species across the taxonomic phyla of Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, and Archaea. The method developed and described herein is a mixed co-culture method that can stably grow more than 50 strains in a single co-culture to generate a DS with more than 50 strains.

[0414] Strains were selected for co-culture based on growth rate, and initially, the production was designed to add strains to the co-culture at different times throughout the production process to achieve optimal growth of each strain. This approach was termed "point-of-addition" production. The rationale behind this initial approach was to ensure that the strains regenerated in the digestive tract to increase the efficacy of engraftment (i.e., to allow engraftment before the strains are excreted). For optimal regeneration and engraftment of lyophilized strains, the strains need to be kept in an "active state" (i.e., active growth state). However, this "point-of-addition" production approach was unsuccessful because the growth rates of the strains in the Consortia described herein were highly variable, making it difficult to simultaneously achieve exponential growth for diverse strains in co-culture. Thus, further experiments were found necessary to understand the unique growth kinetics of each strain to allow for binning of strains based on growth rate and further modification of the addition time point to the bioreactor. Growth kinetic assays were performed using HTP anaerobic growth kinetic assays for each individual strain at eight different inoculation densities in each of Consortia IX-XVI.

[0415] Experiments to understand the unique growth kinetics of each strain proved useful for addition-point manufacturing, but ultimately, the highly variable nature of strains growing in bioreactors from lyophilized powder to active consortia proved undesirable for the addition-point method.

[0416] Based on that, a second approach for co-culture was developed. Instead of applying different addition time points, the second approach used inoculation density adjustment to synchronize growth for each strain, and control of the distribution of strains at the time of harvest from the co-culture ("inoculation density" production). Using the intrinsic growth kinetics determined for each strain in the Consortia, in particular Consortia IX-XVI, the optimal growth zone was determined for each strain. In doing so, it was found that co-culture was effective and possible if each strain was added to the culture based on the inoculation density (i.e., the number of cells per strain added to the co-culture) at the first time point, such that a higher inoculation density of a certain strain results in a shorter growth lag time for such a strain. Based on this, the harvest time point was synchronized as a result of a higher inoculation density for slow-growing strains and a lower inoculation density for fast-growing strains. As shown by example in Figures 2A and 2B, modifying the inoculation density of the individual strains allowed control over the strain distribution and improved strain recovery under co-culture (i.e., an even distribution of strains as well as a higher number of strains recovered is achieved by adjusting the inoculation density). Figure 2A shows an example of a co-culture of 21 fast-growing strains, where only 4 of the 21 strains were not detectable by metagenomic analysis in the final product. However, it is important to note that even if a strain is not detected in the final product, it may still provide a community advantage that allows for more efficient and robust growth of other strains that are detectable in the final product. Figure 2B shows a further modified experiment of the experiment shown in Figure 2A, where the time points of harvest and strain detection were modified. As shown, the different timing of growth and cultivation resulted in a better distribution of strains, with all 21 strains being detected.

[0417] Further modifications of the co-culture process were necessary to improve the fermentation, for example, to control the pH and to achieve growth conditions based on the bioreactor vessel (i.e., vessel type and vessel size).

[0418] Using the methods developed and described herein, Consortia IX-XVI were each produced using only seven DS. One exemplary 7 DS drug product includes three O. formigenes monocultures (see the three phenotypes of the three O. formigenes cultures described in Example 2), a strain in DS1 (e.g., listed in Table 22), a strain in DS2 (e.g., listed in Table 22), a strain in DS3 (e.g., listed in Table 22), and a strain in DS4 (e.g., listed in Table 22).

[0419] Identifying strains were developed to identify each DS without sequencing the entire genome of every strain and to ensure proper growth throughout the co-cultivation process. For DS1, the identifying strains were Bacteroides thetaiotaomicron, Bifidobacterium pseudocatenulatum, and Megasphaera massiliensis. For DS2, the identifying strains were Bacteroides ovatus, Faecalibacterium prausnitzii, and Phascolarctobacterium faecium. For DS3, the identifying strains were Blautia wexlerae, Anaerostipes hadrus, and Clostridium bolteae. For DS4, the identifying strains were Holdemanella biformis, Parasutterella excrementihominis, and Dialister invisus.

[0420] As described herein, the number of strains detected at the end of co-culture may be less than the number of strains added at the beginning of culture.This may be the result of limited detection method.In addition, not all strains can be detected at the end of co-culture process, but the inclusion of undetected strains may still be crucial for the survival and reproduction of other strains that are detected.

[0421] In one experiment, DS1 consisted of 54 initial strains, 50 of which were detected at the end of the co-culture process;DS2 consisted of 47 initial strains, 39 of which were detected at the end of the co-culture process;DS3 consisted of 33 initial strains, 30 of which were detected at the end of the co-culture process;DS4 consisted of 14 initial strains, 11 of which were detected at the end of the co-culture process. Thus, in this experiment, 148 strains were detectable at the beginning of the co-culture and 130 strains were detected at the completion of the culture.

[0422] Obtaining 130 / 148 strains was achieved by developing a fermentation process that allows optimal growth of diverse strains in co-culture. Variables investigated include the growth kinetics of each strain, the nutritional requirements for each strain, the competition for nutrient sources in each DS, and the selection of the optimal starting inoculum concentration to achieve the growth and distribution of strains in each DS. For example, growth curves were performed and used to define the starting inoculum composition as well as the DS buckets. This is shown in Figures 3A and 3B. Figure 3A shows the design of strain separation into four DS buckets based on slow and fast growing strains. Figure 3B shows the starting inoculum seed design for fast and very fast growing strains. Using five iterations of the strain separation and inoculum seed design method, for example, DS1 was able to increase its yield from approximately 35 / 54 strains detected at the end of the co-culture process to 50 / 54 strains detected at the end of the co-culture process.

[0423] Further experimentation was required to successfully produce DS on a large scale. For example, experiments were conducted on the sterilization procedures and raw materials used in the medium, gas solubility in the bioreactor (i.e., fermenter), shear stress caused by the impeller and gas sparging in the bioreactor, and mass transfer and mixing times. Each of these factors is necessary to develop a process that can successfully produce a complex consortia, such as any of the Consortia described herein. For example, experiments found that nitrogen sparging resulted in a higher degree of shear and affected gas solubility. Based on that, experiments were conducted to adjust the sparger speed, sparger position, and replacement of sparging with gas overlay. Data showed that gas overlay was the only technique for successful co-cultivation of DS. For example, data from different sparging conditions only allowed detection of up to 36 of the 54 strains from DS1, whereas gas overlay allowed detection of an additional 11 species (i.e., 47 / 54 strains) at the end of the co-cultivation.

[0424] The next step in the manufacturing process that had to be developed was a way to store the final product in a manner that would preserve the stability and activity of the strains. Freezing and lyophilization methods were investigated to determine what method would preserve the activity and viability of the strains for each DS.

[0425] To determine whether lyophilization is better than freezing to preserve the activity and viability of the strains in each DS, a lyophilization process had to be developed since no lyophilization process was known in the art for the DS and Consortia complexes provided herein. Critical variables investigated to develop a lyophilization process for each DS included, but were not limited to, the formulation of broth or alternative microbiota suspension medium, methods to prevent oxygen contamination during the lyophilization process, excipient:broth ratio, parameters for freezing the microbiota suspension prior to lyophilization, cycle parameters for lyophilization, sterilization requirements, methods for restoring the microbiota after lyophilization storage, buffers for restoring the microbiota, and storage of the lyophilized DS.

[0426] As an example, high-throughput, foil-covered plates were used as one of the storage options tested for lyophilized DS. This was speculated to be effective since the foil cover should prevent oxygen exposure. However, it was found that foil-covered plates did not actually prevent oxygen contamination because there was no way to partially stopper the plates. Another storage method investigated was glass and plastic tray vials with multiple stoppers. It was hypothesized that the theoretical advantage of this approach would be that the multiple stoppers could be pushed into the vials in a single step, allowing high-throughput screening to be performed without the need to individually stopper each vial. However, this method was found to be ineffective as oxygen contamination would occur with the removal of the multiple stoppers. Further options for preserving the lyophilized product were explored and individual glass vials with individual stoppers were found to allow for long-term storage without oxygen contamination.

[0427] As a second example, the exact formulation of the lyophilization buffer / media needed to be determined. The following lyoprotectants were investigated to determine the exact formulation for each DS: sorbitol, maltodextrin, OPS diagnostics buffer, sucrose, inulin, alginate, mannitol, trehalose, and nonfat milk. For example, Figure 4A shows an example of the different viability of DS2 based on different lyoprotectants, and Figure 4B shows an example of the different viability of DS1 based on different lyoprotectants. The addition of reducing agents, including but not limited to cysteine ​​HCL and riboflavin, was also investigated, as shown in Figure 5A (DS2) and Figure 5B (DS1). Additional lyophilized formulations tested included 8% maltodextrin + 0.5% inulin + RA, 5% sucrose + 10% glycerol + 0.3% inulin + RA, 7% trehalose + 8% maltodextrin + RA, 3% sucrose + 5% maltodextrin + 0.5% inulin + RA, 5% maltodextrin + OPS Diag + 0.5% inulin + RA, and 5% maltodextrin + 10% glycerol + 0.3% inulin + RA.

[0428] Based on freeze-thaw and freeze-drying experiments, the data suggested that 10-12% solids was the dose of choice. However, further experiments were performed to determine whether lower doses were possible. One exemplary experiment using DS2 is shown in Figure 6A, and a second exemplary experiment is shown in Figure 6B.

[0429] An assay was then performed to determine the success rate of cell resurrection. Cell resurrection was performed using Anaerobe systems YCFAC medium, and the dilution scheme was performed using a 100-fold dilution for the lyophilized powder (e.g., 50 mg (0.05 g) of powder was diluted in 5.0 mL of YCFAC medium). Resurrection was then detected using flow cytometry and a Coulter counter.

[0430] The experiments performed and data generated here show that freeze-dried material results in comparable colonization of the strains in mice. Example 4 Validation of the EH Mouse Model and Consortia

[0431] As described herein, enteric hyperoxaluria (EH) is caused by excessive absorption of dietary oxalate leading to elevated urinary oxalate (UOx) levels. Once absorbed, oxalate can complex with calcium to form insoluble crystals, and as a result, chronically elevated UOx levels are a major risk factor for the development of kidney stones and progression to kidney damage. There is currently no approved treatment for EH, and standard treatment options are limited to supportive measures and dietary restrictions with relatively low adherence. Most oxalate degradation in the human GI is performed by Oxalobacter formigenes, an obligate human commensal that metabolizes dietary oxalate as its primary energy source. However, it is hypothesized that increased antibiotic utilization and a Western diet have reduced the prevalence of O. formigenes. Preliminary human studies have explored the therapeutic use of orally administered O. formigenes and have demonstrated limited engraftment of O. formigenes, leading to reduced persistence of UOx reduction. Therefore, we reasoned that metabolic support of a diverse consortium of GI commensals would enable O. formigenes engraftment and maximum degradation of oxalate. To this end, microbial consortia that mimic the taxonomic, phylogenetic and functional structure of the healthy human microbiome were designed as described herein. These consortia are not only enriched for O. formigenes to maximize oxalate metabolism, but also contain a large number of bacterial species to support the metabolism of formate, a by-product of oxalate metabolism. In part, these consortia were selected for clinical development by engrafting them in a mouse model of diet-induced hyperoxaluria (HO) and evaluating them there for their ability to reduce UOx.

[0432] Methods: Metagenomic analysis and liquid chromatography-mass spectrometry (LC-MS) were used to assess bacterial species and urinary metabolites, respectively. Metagenomic sequencing was performed on selected fecal samples from each study to assess O. formigenes engraftment, bacterial species richness, and community-specific strain-level engraftment. LC-MS was used to assess oxalate and creatinine levels from final spot urine samples collected.

[0433] Isolation and processing. Isolation of bacterial strains for generating synthetic consortia: Bacterial strains for generating consortia were isolated from healthy human fecal samples collected under anaerobic conditions, homogenized, and then the bacterial species from each sample were identified using whole genome sequencing (WGS). From there, the bacterial strains and their abundance were identified.

[0434] The fecal samples were then processed and bacterial strains were isolated for culture in appropriate culture media (e.g., BHI, blood agar). Strains specific for metabolizing EH-related pathways, with poor isolation of oxalate, were prioritized, along with fastidious and endemic strains, and strains associated with a healthy gut microbiome. After culture, strains were purified and sequenced using metagenomic analysis. From the cultured and isolated strains, a community for treating enteric hyperoxaluria was created based on our bacterial concept of occupying crucial functional niches in the gut, supporting normal GI physiology, supporting the engraftment of specialized strains such as O. formigenes, and degrading oxalate.

[0435] Diversity of synthetic consortia: Consortia were generated to support the engraftment of O. formigenes to the GI. Each consortium contained unique species and strains encompassing various metabolic phenotypes (e.g., bile acid metabolism, short chain fatty acid synthesis, oxalate degradation). The core set of 31 bacterial strains was similar among the synthetic consortia, and each community had its unique signature as shown in the Venn diagram. As shown in Figures 7A and 7B, the number of species present in each generated consortium ranged from 40 to 103 species, and the number of strains ranged from 75 to 195. The species and strains contained various ratios of phylum-level diversity, with the ratio of Bacteroidetes to firmicutes ranging from 51% to 96%, indicating that the general composition differed.

[0436] EH model development. A diet-induced EH mouse model was generated. Dietary components for induction of EH: Three diets (Ox36, 5021 + 0.875% oxalate in drinking water (DW), and 5010 1.51) were made to induce EH with different calorie intake and sodium oxalate in germ-free mice for 3 weeks. Diet 1 (Ox36): Fat (%kcal): 13.5, Carbohydrate (%kcal): 66.0, Protein (%kcal): 20.5, Fiber (%): 6.0, and Sodium Oxalate (g / kg): 3.7. Diet 2 (5021): Fat (%kcal): 23.7, Carbohydrate (%kcal): 53.2, Protein (%kcal): 23.1, Fiber (%): 3.7, and Sodium Oxalate (g / kg): in drinking water. Diet 3 (5010 1.51): Fat (%kcal): 15.0, carbohydrate (%kcal): 54.3, protein (%kcal): 30.6, fiber (%): 4.2, and sodium oxalate (g / kg): 21.5.

[0437] Induction of EH in germ-free and humanized mice: A terminal urine sample was collected to measure UOx (urinary oxalate). BioIVT10 was identified as a potential FMT material for development, and a humanized germ-free model of EH as fecal samples were unable to control oxalate excretion and were devoid of O.formigenes. This fecal sample showed an inability to degrade oxalate when colonized in germ-free mice and when supplemented with O.formigenes, which is capable of degrading oxalate. Additionally, this material showed no presence of O.formigenes. See Figures 8A and 8B.

[0438] Synthetic consortia reduce UOx and lower UOx:UCr ratio in EH-induced mouse model: The three diets described above were tested during the development of microbial consortia to treat EH. All mice were administered 200 μL of each consortium by force-feeding on day 1. Two sets of mice were used: 1) Taconic germ-free C57BL / 6NTac F (7-9 weeks old) that were germ-free, and 2) humanized Taconic germ-free C57BL / 6NTac F (7-9 weeks old). For germ-free mice, dietary EH induction was initiated on D-7, consortia administration was initiated on D1, and the end point of fecal and urine collection was D15. For humanized mice, FMT was administered on D-21, dietary EH induction was initiated on D-14, antibiotic treatment was administered on D-7, consortia administration was initiated on D1, and the end point of fecal and urine collection was D15. Using germ-free mice, it was demonstrated that a significant 3-5 fold increase in urinary oxalate levels was observed across all diets. Furthermore, the 5010 1.51 diet was used in a humanized model in which mice were colonized with FMT. Three different FMT materials, with and without O.formigenes, were used, revealing that FMT in the absence of O.formigenes failed to reduce oxalate degradation compared to controls.

[0439] Synthetic consortia reduce UOx and lower UOx:UCr ratios in EH-induced mouse models. After establishing that hyperoxaluria could be induced in germ-free mice, the question was whether oxalate excretion could or could not be controlled by administration of the consortia described herein. To do so, germ-free mice were induced with hyperoxaluria for 7 days by providing one of the three diets described above, given a single dose of one of the consortia, and then euthanized after 14 days for final urine collection. The diets were spread to effectively induce hyperoxaluria. In general, the consortia described herein reduced the levels of oxalate in the final urine samples collected. Because spot urine samples were collected, the ratio of oxalate to creatinine was calculated as a more robust measure of EH, and the prevalence-based and diversity communities consistently reduced the UOx:UCr ratio across all diets. The average % decline in UOx:UCr across consortia was between 40-55%. See Figure 9.

[0440] As described above, humanized mice were also generated by FMT of germ-free mice using fecal samples that cannot degrade oxalate. These mice were fed a complex high oxalate diet and then pretreated with antibiotics to reduce the host microbiome. After one week of antibiotic administration, the mice were administered one of the consortia described herein. The consortia described herein had different degrees of oxalate reduction.

[0441] Consortia engraftment in various EH-induced models: Engraftment of O. formigenes and other consortia members was assessed using metagenomic sequencing. O. formigenes engrafted to robust levels across all diets tested, with the prevalence-based and diversity communities engrafting at the highest relative abundance. In addition, a greater proportion of strains and species in the prevalence-based and diversity communities engrafted to detectable levels, as shown in the bacterial species richness plots. Finally, the diversity communities had greater bacterial species richness compared to five rationally designed synthetic consortia created with varying degrees of diversity by enriching O. formigenes from donor fecal samples to control for oxalate metabolism at GI tract baseline in the "humanized" model. This indicates that in the composite model, the diversity communities stably engrafted germ-free mice and replaced the human communities already established there. See Figures 10A, 10B, 10C and 10D.

[0442] Based on these experiments, the five rationally designed synthetic consortia in this experiment were found to have different degrees of diversity and to be able to control oxalate metabolism in the GI tract to different degrees. It was further revealed that the diverse consortia described herein can engraft after administration. Specifically, the experiments described herein show that O. formigenes was one of the microorganisms that could engraft. Furthermore, it was revealed that the consortia described herein can reduce oxalate excretion (UOx and UOx:UCr ratio) to different degrees in the diet-induced EH model, and that the consortium with the greatest diversity, community V, described in this Example 5, has the ability to stably engraft O. formigenes, therapeutically reduce UOx, and result in a healthy human microbiome. Example 5 Preparation of threonine auxotrophic microorganisms

[0443] Certain microorganisms are auxotrophs. This means that they are unable to synthesize certain organic compounds necessary for their growth. One such organic compound that certain microorganisms themselves are unable to synthesize is threonine. Furthermore, some microorganisms are not themselves auxotrophs for threonine, but are inefficient producers of threonine, which prevents effective growth in commonly used growth media.

[0444] N-acetylgalactosamine (GalNAc) is an amino sugar derivative of galactose, which is typically the first monosaccharide that connects serine or threonine in certain forms of protein O-glycosylation. Although it is possible to supplement certain small-batch growth media with GalNAc to grow threonine auxotrophs without added threonine, such supplementation is not preferred for large-batch production because GalNAc is expensive and large quantities are required for effective growth of microorganisms that require such galactose derivatives. Furthermore, certain media, such as YCFAC medium, are unable to effectively grow certain threonine auxotrophs even in the presence of GalNAc.

[0445] Therefore, methods to improve the expansion and growth of inefficient producers of threonine are needed to effectively grow such microorganisms.

[0446] One such microorganism included in the consortium described herein is Akkermansia muciniphilia.Akkermansia cannot synthesize threonine by itself, and therefore cannot effectively expand and grow in cultures that lack a GalNac source (or a primary source that can be metabolized to GalNac).Furthermore, GalNac is the preferred carbon source of Akkermansia, and therefore the known method of effectively growing and producing Akkermansia includes adding GalNac to the growth medium.

[0447] Therefore, an experiment was designed to identify a novel way to grow Akkermansia in large batches without large amounts of GalNac. Specifically, three different growth media were tested: YCFAC+GalNac, YCFAC+GalNac+threonine, and YCFAC+threonine. BHI medium was used as a positive control (specifically, BHI medium+GalNac+hemin+vitamin K), since BHI is an animal-based medium that contains threonine. GalNac is expected to be required to allow the expansion and growth of the microorganisms in all media, since it is the preferred carbon source for Akkermansia, but the question anticipated was how much GalNac would be required if threonine was also added, or if GalNac would not be required at all. Surprisingly, we found that 1) YCFAC + 0.5 g / L GalNac did not support Akkermansia growth, 2) YCFAC + 0.5 g / L GalNac + 10 mM threonine did support growth, and 3) YCFAC + 10 mM threonine alone supported Akkermansia growth. In these experiments, seed cultures containing 0.5 g / L GalNac in YCFAC were used to initiate cell growth before being transferred to larger fermentors for growth and expansion in the three media described above.

[0448] However, some of the consortia described herein contain more than 100 different microorganisms, with Akkermansia being only one of the more than 100 different microorganisms. Furthermore, the production methods described herein allow for the growth and production of multiple microorganisms in a single large batch culture (e.g., in a fermenter). The question then was, how do you grow Akkermansia in a large co-culture when it is the only microorganism that is a threonine auxotroph with a preferred carbon source of GalNac? Therefore, an experiment was designed to determine whether it would be possible to start a seed culture with just Akkermansia and then combine it with a second seed culture of multiple microorganisms for large batch expansion.

[0449] The experiment included: 1) first growing a seed culture to initiate growth of Akkermansia in a 10 mL small culture (i.e., seed culture) prior to expansion to a larger batch fermentor, 2) growing a second 100 mL seed culture of all other microorganisms in the drug substance independently in parallel with the Akkermansia seed culture, 3) combining the 100 mL seed co-culture and the 10 mL Akkermansia seed culture into a larger batch fermentor (e.g., 1 L or larger), and 4) evaluating the ability of Akkermansia to detect strains of the drug substance and grow and expand in co-culture. A schematic of this experiment is shown in Figure 11A.

[0450] It was surprising to find that Akkermansia was unable to grow in YCFAC medium supplemented with GalNac, hemin and vitamin K (0.0000% Akkermansia detected) compared to BHI medium supplemented with GalNac, hemin and vitamin K, as shown in Figure 12. The results showed that YCFAC+GalNAc was unable to support the growth of Akkermansia. The question then was whether the addition of threonine could restore the growth of Akkermansia.

[0451] The next question was whether GalNAc was necessary when threonine was added. Specifically, the question was how Akkermansia would grow in YCFAC+10 mM threonine (72 hour growth) compared to YCFAC+10 mM threonine+0.5 g / L GalNAc (48 hour growth). It was surprising to find that the results showed comparable growth with and without GalNAc (OD of 0.25 without GalNAc and 0.35 with GalNAc).

[0452] A co-culture experiment similar to that described above and shown in FIG. 11A was designed to evaluate the requirement for GalNAc and threonine. In this experiment, two seed cultures were used: 1) Akkermansia seeds grown in YCFAC+10 mM threonine+0.5 g / L GalNAc, and 2) other microorganisms in the drug substance (14 microorganisms) grown in YCFAC only. The seed cultures were then combined into a large batch fermenter containing YCFAC+10 mM threonine (i.e., no GalNAc). See FIG. 11B. This study showed that Akkermansia does not require GalNAc to grow in co-culture with other microorganisms that are not threonine auxotrophs in the presence of 10 mM threonine in the large batch fermenter. Furthermore, in 10 mM threonine YCFAC medium, Akkermansia was detected at all growth time points (FIG. 13).

[0453] Further experiments showed that GalNAc was not required in seed cultures to achieve Akkermansia growth.

[0454] The ability to grow Akkermansia without GalNAc was quite surprising given that GalNAc is the preferred carbon source for Akkermansia, and furthermore, the ability to grow Akkermansia in GalNAc-free medium provides a means to grow Akkermansia in multi-microbial co-cultures and generate GalNAc-containing microbial pharmaceuticals. Example 6 Clinical Candidate Selection

[0455] As described above, Consortia IX was selected as a clinical candidate for clinical trials and named FB-001. FB-001 contains 148 different anaerobic microbial strains designed to mimic the metabolic and phylogenetic diversity of the human microbiome (Figure 17) and separated into seven different drug substances for manufacturing purposes. Table 22 shows the seven different drug substances. Species were identified by 16S rRNA gene sequencing and whole genome sequencing of the RCB. The species in the consortium span six of the major phyla found in the GI tract of healthy adults (King, Desai et al. 2019), with the deliberate exclusion of Fusobacteria, a phylum commonly associated with human infections and rich in opportunistic pathogens. The 148 strains encompass 10 distinct classes, 18 orders, 26 families, and 59 genera.

[0456] Prior to lyophilization, the cell pellet containing the FB-001 microbial strain was resuspended in YCFAC medium with lyoprotectant and then lyophilized. The YCFAC medium and lyoprotectant were selected to stabilize the DS during the lyophilization step. The lyoprotectant combination of 8% maltodextrin + 0.5% inulin was selected for the final DS formulation because it showed high survival rate of the FB-001 microbial strain in formulation development studies.

[0457] Maltodextrin was also added as a bulking agent during DP production.

[0458] The capsules for encapsulating the DP were enterically coated and selected to release the DP in the small intestine and to resist stomach acid as it passes through the digestive tract. Dissolution of these capsules was measured at a pH of 1.2 according to USP <701> and showed no disintegration for 2 hours. The capsules completely disintegrated within 30 minutes at a pH of 6.8, which is the target release pH in the GI tract for FB-001 DP (hydroxypropyl methylcellulose [HPMC] capsule COA).

[0459] Functional Properties of FB-001. FB-001 was manufactured using seven individual drug substances (DS) containing a total of 148 anaerobic microbial strains, enriched for species that perform beneficial or normalizing functions in the human GI tract.

[0460] The first of these beneficial or normalizing functions is oxalate degradation, which is the primary EH disease-modifying mechanism of FB-001. Oxalobacter formigenes is the primary driver of oxalate degradation in the human GI tract. O. formigenes uses oxalate as its exclusive energy source and thus metabolizes significant concentrations of oxalate for energy generation and biomass production. Oxalate metabolism is mediated by a series of enzymes and transport reactions that ultimately consume oxalate and release CO2 and formate.

[0461] Formate, as a by-product of oxalate metabolism, can ultimately inhibit further oxalate metabolism in vitro if it is not removed. Therefore, FB-001 also contains strains that can degrade formate. These formate-utilizing bacteria help to remove potentially inhibitory metabolic by-products of oxalate metabolism.

[0462] FB-001 also contains strains that are oxalate resistant, and are able to grow in the presence of oxalate concentrations above a certain size or physiologically normal concentration of oxalate. This enrichment of oxalate resistant strains in the FB-001 consortium can support stable engraftment despite potentially high levels of free oxalate in the GI lumen of patients with EH, as the abundance of essential oxalotrophs will naturally increase with increasing oxalate concentrations.

[0463] Specifically, the FB-001 consortium was designed to contain phylogenetically diverse microbial species that function symbiotically to maximize metabolic flux of oxalate (primary mechanism) and ameliorate malabsorption-associated dysbiosis (secondary mechanism). To ensure the implementation of both mechanisms, the FB-001 consortium contains numerous oxalate-degrading strains to reduce free oxalate concentrations in the GI tract, as well as a large number of species aimed at supporting the community by restoring essential metabolic functions that alleviate malabsorption of any undegraded oxalate. The strains that make up the FB-001 consortium were selected based on their predicted ability to perform various supporting metabolic functions that contribute to engraftment without regard for differences in patient physiology or diet. Metabolism of macronutrients and dietary molecules that are not digested or utilized by the host cells can result in the release of metabolites that feed other members of the microbiome community.

[0464] Other strains in FB-001 were evaluated for their unique and potentially beneficial biological functions in the GI tract, including short chain fatty acid (SCFA) production, syntrophic activity, and mucin degradation. SCFAs are recognized to be absorbed by the host and confer a variety of health-promoting functions by acting as vital energy substrates for colonocytes, enterocytes, and hepatocytes, while also acting as signaling molecules recognized by specific G-protein couple receptors that primarily target enteroendocrine and immune cells in the lamina propria of the intestinal mucosa. Strains in FB-001 were evaluated for their syntrophic activity, a process by which bacteria make by-products that serve as food for other bacteria. Syntrophic activity stabilizes the gut microbiome and creates novel niches. Strains in FB-001 were also evaluated for putative protective and / or anti-inflammatory properties.

[0465] Table 23 summarizes the number of strains in FB-001 that contribute to each of these functional properties, and Table 24 summarizes the characteristics associated with each FB-001 species.

[0466] [Table 23]

[0467] [Table 24-1] [Table 24-2]

[0468] Formate metabolism. The FB-001 DP consortium also contains formate-utilizing bacteria to maintain maximum carbon flux in the pathway. Formate, as a by-product of oxalate metabolism, can ultimately inhibit further oxalate metabolism in vitro if it is not removed. Mutualistic bacterial species such as methanogens found in the human GI tract can efficiently remove formate by reduction to methane in the presence of hydrogen gas produced by microbial fermenters. Thus, the FB-001 Consortia includes Methanobrevibacter smithii (DS-CoC2), the most common and abundant archaeal methanogen in the gut that efficiently metabolizes formate, as well as the acetogenic gut symbiont Blautia hydrogenotrophica (DS-CoC1), which utilizes formate to produce acetate for short-chain fatty acid (SCFA) synthesis, and a panel of anaerobes expressing cytochrome-dependent formate dehydrogenase that oxidizes formate to CO2 (e.g., Sutterella and Parasutterella, found in DS-CoC2 and DS-CoC4). These formate-utilizing bacteria thus help to remove potentially inhibitory metabolic by-products of oxalate metabolism.

[0469] Supportive metabolic functions. FB-001 also contains a diverse panel of broad-functional commensals that perform unique and potentially beneficial biological functions in the GI tract, including macronutrient metabolism, short chain fatty acid production, syntrophic activity and mucin degradation.

[0470] Composition of FB-001 DP. The FB-001 DP is a highly complex mixed fermentation of 148 microbial strains selected for their potential role in supporting a healthy GI tract. To support clinical research, metagenomic sequencing was used to characterize the FB-001 DP for the relative abundance of individual species in the final DP, as well as for the total O. formigenes content. Metagenomic sequencing and analysis first confirmed that strains were present in the sample by positive identification of pre-specified biomarkers (short sequences of DNA) that were unique to the strain of interest. Metagenomic sequencing results were then reported as the relative abundance of each strain, approximating the percentage of genome copies that belong to each strain and which could range from 0 to 100%. Relative abundance was then calculated by comparing the number and frequency of detected biomarkers to the total number of strain-specific biomarkers and the number of sequencing reads. The percent contribution of each strain in the FB-001 DP included a major portion of three O. formigenes strains identified by 16S RNA and carbon source analyses described below, as follows: approximately 32% O. formigenes on a relative abundance basis (i.e., approximately 40% on a viable cell count basis) and 145 other strains with relative abundance values ​​ranging from 18% to 0.015%, a typical distribution of the human microbiome.

[0471] FB-001 DP was manufactured as a single batch. Single capsules in DP form were collected and stored at -20°C ± 5 until DNA extraction. FB-001 DP was sequenced by shotgun metagenomic analysis and metagenomic sequences of DP were analyzed to determine the composition of FB-001 DP. Results were reported as the relative abundance of each strain. Relative abundance approximates the percentage of FB-001 DP genome copies that belong to each strain and can range from 0 to 100%. A total of 60 of the 148 strains were detected at or above their quantitative detection limits, including 21 strains fr...

Claims

1. A pharmaceutical composition comprising: (a) (i) Clostridium citroniae, Bacteroides saliersiae, Blautia obeum, Parabacteroides merdae, Parabacteroides distasonis, Anaerotypes hadrus, Lachnospiraceae sp. FBI00033, Eubacterium eligens, Bifidobacterium dentium, Blautia wexlerae, Fusicatenibater saccharivorans, Bacteroides nordii, Dorea formicigenans, Dorea longicatena, Bacteroides stercorirosoris, Bifidobacterium longum, Bacteroides kribbi, Lachnospiraceae sp. FBI00071, Bacteroides thetaiotaomicron, Clostridium clostridioforme, Clostridium scindens, Roseburia hominis, Clostridium fessum, Coprococcus comes, Blautia faecis, Hungatella hathawayi, Bacteroides stercoris, Collinsella aerofaciens, Hungatella effluvii, Bifidobacterium adolescentis, Bifidobacterium catenulatum, Lactobacillus rogosa, Bacteroides faeces, Bacteroides finegoldii, Clostridium sp. FBI00191, Ruminococcus faeces, Lachnoclostridium pacaense, Clostridium boltea, Longicathena caecimuris, Eggerthella lenta, Blautia massiliensis, Bacteroides xylanisolvens, Bacteroides vulgatus, MegasphereMassilensis, Butyricimonas faecihominis, Eisenbergiella tayi, Acidaminococcos intestini, Emergence timonensis, Bifidobacterium pseudocatenulatum, Eubacterium hallii, Anaerofustis stercorihominis, Eubacterium ventriosum, Blautia hydrogenotrophica, Lachnospiraceae sp (ii) FBI00001, FBI00002, FBI00010, FBI00013, FBI00029, FBI00032, FBI00 033, FBI00034, FBI00043, FBI00044, FBI00048, FBI00050, FBI00051, FBI00 057, FBI00059, FBI00060, FBI00070, FBI00071, FBI00076, FBI00079, FBI00 087, FBI00093, FBI00102, FBI00109, FBI00117, FBI00120, FBI00125, FBI001 27, FBI00128, FBI00145, FBI00162, FBI00174, FBI00184, FBI00190, FBI00191, FBI00194, FBI00198, FBI00199, FBI00200, FBI00201, FBI00205, FBI00206, FBI00211, FBI00220, FBI00221, FBI00236, FBI00245, FBI00248, FBI00251, FBI00254, FBI00267, FBI00278, FBI00288, and FBI00290, or their functional equivalents. A consortium including; (b) (i) Acute bacterium timonensis, Alistipes onderdonkii, Bacteroides uniformis, Eubacterium rectale, Alistipes timonensis, Bacteroides kribbi, Coprococcus eutactus, Bilophila wadsworthia, Bacteroides caccae, Alistipes shahii, Parasutterella Excrement hominis, Paraprevotella clara, Sutterella wadsworthensis, Sutterella massiliensis, Porphyromonas asaccharolytica, Ruminococcus bromii, Monoglobus pectinilyticus, Ruminococcaceae sp. FBI00097, Gordonibacter pamelaeae, Bacteroides uniformis, Gordonibacter pamelaea, Bacteroides fragilis, Phascolarctobacterium faecium, Monoglobus pectinolyticus, Clostridium aldenense, Ruthenibacterium lactatiformans, Bacteroides ovatus, Bifidobacterium bifidum, Anaerotruncus massiliensis, Clostridium aldenense, Sutterella wadsworthensis, Catabacter hongkongensis, Alistipes senegalensis, Ruminococcaceae sp. FBI00233, Alistipes shahii, Dielma fastidiosa, Eubacterium siraeum, Faecalibacterium prausnitzii, Turicibacter sanguinis, Eubacterium rectale, Bacteroides caccae, Methanobrevibacter smythii、Brnesimlstintestinihominis, Alistipes onderdonkii, Methanobrevibacter smithii, or functional equivalents thereof, or (ii) FBI00004, FBI00012, FBI00015, FBI00018, FBI00019, FBI00021, FBI00038, FBI00040, FBI00046, FBI00061, FBI00066, FBI 00075, FBI00077, FBI00080, FBI00081, FBI00085, FBI00092, FBI00097, FBI00099, FBI00112, FBI00132, FBI00137, FBI00140, FB I00149, FBI00151, FBI00176, FBI00189, FBI00197, FBI00208, FBI00212, FBI00224, FBI00226, FBI00229, FBI00233, FBI00235, FBI00237, FBI00243, FBI00244, FBI00258, FBI00260, FBI00263, FBI00270, FBI00273, FBI00277, and FBI00292, or their functional equivalents. A consortium including; (c) (i) Bifidobacterium adolescentis, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bacteroides thetaiotaomicron, Coprococcus comes, Fusicatenibacter saccharivorans, Eggerthella lenta, Eubacterium elegans, Bacteroides xylanisolvens, Lactobacillus rogosae, Clostridium citroniae, Collinsella aerofaciens, Blautia obeum, Eggerthella lenta, Blautia wexlerae, Lachnoclostridium pacaense, Bacteroides vulgatus, Parabacteroides merdae, Dorea formicigenans, Ruminococcus faecis, Roseburia hominis, Anaerotypes hadrus、Bifidobacteriumm adolescentis、｢ifidobacteriumm pseudocatenulatumm、Clostridium bolteae、Eisenbergiella tayi、Dorea longicatena、Eggerthella lenta、Bacteroides stercoris、Hungatella hathawayi、Bacteroides xylanisolvens、or their functional equivalents、or (ii) FBI00009, FBI00011, FBI00016, FBI00020, FBI00025, FBI00027, FBI00030, FBI00047 , FBI00052, FBI00053, FBI00056, FBI00062, FBI00078, FBI00096, FBI00104, FBI00110, FB I00111, FBI00113, FBI00115, FBI00116, FBI00123, FBI00124, FBI00126, FBI00135, FBI00147, FBI00159, FBI00167, FBI00170, FBI00232, FBI00255, and FBI00271, or their functional equivalents. A consortium including; (d) (i) Alistipes putredinis, Dialister succinatiphilus, Akkermansia muciniphila, Ruminococcus bromii, Dialister invisus, Bacteroides massiliensis, Bilophila wadsworthia, Holdemanella biformis, Parasutterella excrementihominis, Alistipes sp. FBI00180, Bacteroides coprocola, Alistipes sp. FBI00238, Alistipes putredinis, Eubacterium xylanophilum, Senegalimassilia anaerobia, or functional equivalents thereof, or (ii) FBI00022, FBI00049, FBI00068, FBI00069, FBI00152, FBI00165, FBI00171, FBI00175, FBI00177, FBI00180, FBI00182, FBI00238, FBI00269, FBI00274, and FBI00281, or functional equivalents thereof. a consortium including; or (e) Combinations thereof A pharmaceutical composition comprising:

2. (a) each strain is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:83 , SEQ ID NO:89, SEQ ID NO:94, SEQ ID NO:100, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:123, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:136, SEQ ID NO:143, SEQ ID NO:145, or SEQ ID NO:147; (b) each strain comprises a 16s RNA nucleotide sequence identical to the nucleotide sequence set forth in SEQ ID NO:3, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:27, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:66, SEQ ID NO:78, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:96, SEQ ID NO:101, SEQ ID NO:105, SEQ ID NO:112, SEQ ID NO:114, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:138, SEQ ID NO:140, SEQ ID NO:142, or SEQ ID NO:148; or (c) each strain comprises a 16s RNA nucleotide sequence identical to the nucleotide sequence set forth in SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:10, SEQ ID NO:13, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:28, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:40, SEQ ID NO:50, SEQ ID NO:58, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:88, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:120, SEQ ID NO:132, or SEQ ID NO:139; or (d) each strain comprises a 16s RNA nucleotide sequence identical to the nucleotide sequence set forth in SEQ ID NO:15, SEQ ID NO:30, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:87, SEQ ID NO:90, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:125, SEQ ID NO:137, SEQ ID NO:141, or SEQ ID NO:144; or (e) each strain includes a combination thereof; The composition of claim 1.

3. The composition of claim 1, further comprising at least one oxalate-metabolizing microbial strain, wherein the at least one strain expresses an enzyme selected from formyl-CoA transferase, oxalate-formate exchanger, and oxalyl-CoA decarboxylase.

4. The method of claim 1, wherein the at least one oxalate-metabolizing microbial strain comprises: (a) a first O. formigenes strain FBI00067, or a functional equivalent thereof; (b) a second O. formigenes strain FBI00133, or a functional equivalent thereof; (c) a third O. formigenes strain FBI00289, or a functional equivalent thereof; or (d) Combinations thereof The composition of claim 3 selected from:

5. The composition described in claim 4, wherein each strain contains a 16s RNA nucleotide sequence identical to the nucleotide sequence set forth in SEQ ID NO: 42, SEQ ID NO: 79, or SEQ ID NO:

146.

6. The composition of claim 1, comprising about 5×10 10 to about 5×10 11 live cells, about 5×10 9 to about 5×10 10 live cells, about 5×10 11 to about 5×10 12 live cells, or a maximum of about 5×10 12 live cells.

7. A microbial consortium comprising a microbial strain listed in Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, Table 10, Table 11, Table 12, Table 13, Table 14, Table 15, Table 16, Table 17, Table 18, Table 19, or Table 22, or a functional equivalent thereof.

8. A microbial consortium as described in claim 7, wherein each strain contains a 16s RNA nucleotide sequence identical to a nucleotide sequence set forth in SEQ ID NOs: 1 to 148.

9. A method for producing a composition, comprising: (a) (i) Clostridium citroniae, Bacteroides saliersiae, Blautia obeum, Parabacteroides merdae, Parabacteroides distasonis, Anaerotypes hadrus, Lachnospiraceae sp. FBI00033, Eubacterium eligens, Bifidobacterium dentium, Blautia wexlerae, Fusicatenibater saccharivorans, Bacteroides nordii, Dorea formicigenans, Dorea longicatena, Bacteroides stercorirosoris, Bifidobacterium longum, Bacteroides kribbi, Lachnospiraceae sp. FBI00071, Bacteroides thetaiotaomicron, Clostridium clostridioforme, Clostridium scindens, Roseburia hominis, Clostridium fessum, Coprococcus comes, Blautia faecis, Hungatella hathawayi, Bacteroides stercoris, Collinsella aerofaciens, Hungatella effluvii, Bifidobacterium adolescentis, Bifidobacterium catenulatum, Lactobacillus rogosa, Bacteroides faeces, Bacteroides finegoldii, Clostridium sp. FBI00191, Ruminococcus faeces, Lachnoclostridium pacaense, Clostridium boltea, Longicathena caecimuris, Eggerthella lenta, Blautia massiliensis, Bacteroides xylanisolvens, Bacteroides vulgatus, MegasphereMassilensis, Butyricimonas faecihominis, Eisenbergiella tayi, Acidaminococcos intestini, Emergence timonensis, Bifidobacterium pseudocatenulatum, Eubacterium hallii, Anaerofustis stercorihominis, Eubacterium ventriosum, Blautia hydrogenotrophica, Lachnospiraceae sp (ii) FBI00001, FBI00002, FBI00010, FBI00013, FBI00029, FBI00032, FBI00 033, FBI00034, FBI00043, FBI00044, FBI00048, FBI00050, FBI00051, FBI00 057, FBI00059, FBI00060, FBI00070, FBI00071, FBI00076, FBI00079, FBI00 087, FBI00093, FBI00102, FBI00109, FBI00117, FBI00120, FBI00125, FBI001 27, FBI00128, FBI00145, FBI00162, FBI00174, FBI00184, FBI00190, FBI00191, FBI00194, FBI00198, FBI00199, FBI00200, FBI00201, FBI00205, FBI00206, FBI00211, FBI00220, FBI00221, FBI00236, FBI00245, FBI00248, FBI00251, FBI00254, FBI00267, FBI00278, FBI00288, and FBI00290, or their functional equivalents. obtaining a first consortium comprising: (b) (i) Acute bacterium timonensis, Alistipes onderdonkii, Bacteroides uniformis, Eubacterium rectale, Alistipes timonensis, Bacteroides kribbi, Coprococcus eutactus, Bilophila wadsworthia, Bacteroides caccae, Alistipes shahii, Parasutterella Excrement hominis, Paraprevotella clara, Sutterella wadsworthensis, Sutterella massiliensis, Porphyromonas asaccharolytica, Ruminococcus bromii, Monoglobus pectinilyticus, Ruminococcaceae sp. FBI00097, Gordonibacter pamelaeae, Bacteroides uniformis, Gordonibacter pamelaea, Bacteroides fragilis, Phascolarctobacterium faecium, Monoglobus pectinolyticus, Clostridium aldenense, Ruthenibacterium lactatiformans, Bacteroides ovatus, Bifidobacterium bifidum, Anaerotruncus massiliensis, Clostridium aldenense, Sutterella wadsworthensis, Catabacter hongkongensis, Alistipes senegalensis, Ruminococcaceae sp. FBI00233, Alistipes shahii, Dielma fastidiosa, Eubacterium siraeum, Faecalibacterium prausnitzii, Turicibacter sanguinis, Eubacterium rectale, Bacteroides caccae, Methanobrevibacter smythii、Brnesimlstintestinihominis, Alistipes onderdonkii, Methanobrevibacter smithii, or functional equivalents thereof, or (ii) FBI00004, FBI00012, FBI00015, FBI00018, FBI00019, FBI00021, FBI00038, FBI00040, FBI00046, FBI00061, FBI00066, FBI 00075, FBI00077, FBI00080, FBI00081, FBI00085, FBI00092, FBI00097, FBI00099, FBI00112, FBI00132, FBI00137, FBI00140, FB I00149, FBI00151, FBI00176, FBI00189, FBI00197, FBI00208, FBI00212, FBI00224, FBI00226, FBI00229, FBI00233, FBI00235, FBI00237, FBI00243, FBI00244, FBI00258, FBI00260, FBI00263, FBI00270, FBI00273, FBI00277, and FBI00292, or their functional equivalents. obtaining a second consortium comprising: (c) (i) Bifidobacterium adolescentis, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bacteroides thetaiotaomicron, Coprococcus comes, Fusicatenibacter saccharivorans, Eggerthella lenta, Eubacterium elegans, Bacteroides xylanisolvens, Lactobacillus rogosae, Clostridium citroniae, Collinsella aerofaciens, Blautia obeum, Eggerthella lenta, Blautia wexlerae, Lachnoclostridium pacaense, Bacteroides vulgatus, Parabacteroides merdae, Dorea formicigenans, Ruminococcus faecis, Roseburia hominis, Anaerotypes hadrus、Bifidobacteriumm adolescentis、｢ifidobacteriumm pseudocatenulatumm、Clostridium bolteae、Eisenbergiella tayi、Dorea longicatena、Eggerthella lenta、Bacteroides stercoris、Hungatella hathawayi、Bacteroides xylanisolvens、or their functional equivalents、or (ii) FBI00009, FBI00011, FBI00016, FBI00020, FBI00025, FBI00027, FBI00030, FBI00047 , FBI00052, FBI00053, FBI00056, FBI00062, FBI00078, FBI00096, FBI00104, FBI00110, FB I00111, FBI00113, FBI00115, FBI00116, FBI00123, FBI00124, FBI00126, FBI00135, FBI00147, FBI00159, FBI00167, FBI00170, FBI00232, FBI00255, and FBI00271, or their functional equivalents. obtaining a third consortium comprising: (d) (i) Alistipes putredinis, Dialister succinatiphilus, Akkermansia muciniphila, Ruminococcus bromii, Dialister invisus, Bacteroides massiliensis, Bilophila wadsworthia, Holdemanella biformis, Parasutterella excrementihominis, Alistipes sp. FBI00180, Bacteroides coprocola, Alistipes sp. FBI00238, Alistipes putredinis, Eubacterium xylanophilum, Senegalimassilia anaerobia, or functional equivalents thereof, or (ii) FBI00022, FBI00049, FBI00068, FBI00069, FBI00152, FBI00165, FBI00171, FBI00175, FBI00177, FBI00180, FBI00182, FBI00238, FBI00269, FBI00274, and FBI00281, or functional equivalents thereof. obtaining a fourth consortium comprising: (e) blending the first consortium, the second consortium, the third consortium, and the fourth consortium, thereby obtaining the composition; A method comprising:

10. The method described in claim 9, wherein the fourth composition is obtained by growing a microorganism in the presence of threonine.

11. The method described in claim 9 or 10, wherein the composition comprises a lyoprotectant, maltodextrin, inulin, or a combination thereof.

12. (a) obtaining a fifth consortium comprising the first O. formigenes strain FBI00067, or a functional equivalent thereof; (b) obtaining a sixth consortium comprising a second O. formigenes strain FBI00133, or a functional equivalent thereof; (c) obtaining a seventh consortium comprising the third O. formigenes strain FBI00289, or a functional equivalent thereof; and (d) blending the fifth consortium, the sixth consortium, and the seventh consortium with the composition.

10. The method of claim 9, further comprising:

13. The method of claim 9, wherein (a) each consortium is freeze-dried separately before blending, (b) each consortium is prepared using inoculation density adjustment, and / or (c) each consortium is cultured or has been cultured in the presence of a gas overlay or in the absence of gas sparging.

14. A composition prepared by the method of claim 9.

15. A dose for enteral administration comprising a composition according to any one of claims 1 to 6 or 14.

16. A dosage for oral administration comprising a composition according to any one of claims 1 to 6 or 14.

17. A composition according to any one of claims 1 to 6 or 14 for use in treating hyperoxaluria, reducing the risk of developing hyperoxaluria, and / or reducing urinary oxalate in a subject in need thereof.

18. A composition for use as described in claim 17, wherein the hyperoxaluria is primary hyperoxaluria, secondary hyperoxaluria, or enteric hyperoxaluria.

19. A kit comprising a composition described in any one of claims 1 to 6 or 14.

20. A method for culturing a microbial strain from the genus Akermansia, comprising contacting said strain with N-acetylgalactosamine (GalNAc).

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