Methods and compositions relating to microbial treatment and diagnosis of disorders

Abstract

The present disclosure provides methods, systems, compositions, and kits to address the need for microbiome-related treatment of health conditions and disease. The present disclosure provides for treatment of metabolic conditions using microbial compositions.

1 - 20 . (canceled) 
     
     
         21 . A method of treating a disorder, the method comprising: administering to a subject in need thereof a pharmaceutical composition comprising a pharmaceutically-acceptable carrier and a therapeutically-effective amount of a population of isolated and purified microbes, wherein at least one of said microbes comprises a gene that encodes for an enzyme selected from the group consisting of: butyrate kinase and butyryl Coenzyme A:acetoacetate Coenzyme A transferase. 
     
     
         22 . The method of  claim 21 , wherein the disorder is selected from the group consisting of: metabolic disorder, obesity, diabetes, skin disorder, inflammation, gut permeability disorder, and neurological disorder. 
     
     
         23 . The method of  claim 21 , wherein said population of isolated and purified microbes comprises a microbe with a rRNA sequence comprising at least about 85% sequence identity to a rRNA sequence of a microbe selected from the group consisting of:  Akkermansia muciniphila, Anaerostipes caccae, Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum, Clostridium aminophilum, Clostridium beijerinckii, Clostridium butyricum, Clostridium colinum, Clostridium indolis, Clostridium orbiscindens, Enterococcus faecium, Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii, Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus caucasicus, Lactobacillus fermentum, Lactobacillus helveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburia cecicola, Roseburia inulinivorans, Ruminococcus flavefaciens, Ruminococcus gnavus, Ruminococcus obeum, Streptococcus cremoris, Streptococcus faecium, Streptococcus infantis, Streptococcus mutans, Streptococcus thermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus, Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani, Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacterium dolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis, Roseburia intestinalis , and any combination thereof. 
     
     
         24 . The method of  claim 23 , wherein said population of isolated and purified microbes comprises at least two different microbial strains, wherein the microbial strain comprises at least about 85% sequence identity to a rRNA sequence of a microbe selected from the group consisting of:  Akkermansia muciniphila, Anaerostipes caccae, Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum, Clostridium aminophilum, Clostridium beijerinckii, Clostridium butyricum, Clostridium colinum, Clostridium indolis, Clostridium orbiscindens, Enterococcus faecium, Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii, Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus caucasicus, Lactobacillus fermentum, Lactobacillus helveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburia cecicola, Roseburia inulinivorans, Ruminococcus flavefaciens, Ruminococcus gnavus, Ruminococcus obeum, Streptococcus cremoris, Streptococcus faecium, Streptococcus infantis, Streptococcus mutans, Streptococcus thermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus, Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani, Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacterium dolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis, Roseburia intestinalis , and any combination thereof. 
     
     
         25 . The method of  claim 21 , wherein the administration is oral. 
     
     
         26 . The method of  claim 21 , wherein the pharmaceutical composition comprises an enteric-coating that dissolves at a pH greater than about pH 6.5. 
     
     
         27 . The method of  claim 21 , wherein the pharmaceutical composition is delivered to a small intestine, an ileum, a large intestine, or a combination thereof of a human subject. 
     
     
         28 . The method of  claim 21 , wherein the pharmaceutical composition further comprises a prebiotic. 
     
     
         29 . The method of  claim 28 , wherein the prebiotic is selected from the group consisting of: complex carbohydrate, complex sugar, resistant dextrin, resistant starch, amino acid, peptide, nutritional compound, biotin, polydextrose, fructooligosaccharide (FOS), galactooligosaccharide (GOS), inulin, starch, lignin, psyllium, chitin, chitosan, gum, guar gum, high amylose cornstarch (HAS), cellulose, β-glucan, hemi-cellulose, lactulose, mannooligosaccharide, mannan oligosaccharide (MOS), oligofructose-enriched inulin, oligofructose, oligodextrose, tagatose, trans-galactooligosaccharide, pectin, resistant starch, xylooligosaccharide (XOS), carrageenan, and any combination thereof. 
     
     
         30 . The method of  claim 21 , wherein the pharmaceutical composition is administered before food intake, with food intake, or both to the subject. 
     
     
         31 . The method of  claim 21 , wherein the therapeutically-effective amount of the purified and isolated microbes in the pharmaceutical composition is at least about 10 5  colony forming units (CFU). 
     
     
         32 . The method of  claim 21 , wherein the pharmaceutical composition is administered after completion of an antibiotic regimen by the subject. 
     
     
         33 . The method of  claim 21 , wherein the population of isolated and purified microbes comprises a first microbe and a second microbe, wherein the first microbe produces an intermediate compound of a butyrate pathway, wherein the second microbe converts the intermediate compound to butyrate. 
     
     
         34 . The method of  claim 33 , wherein the intermediate compound is lactate or acetate. 
     
     
         35 . The method of  claim 21 , wherein the population of isolated and purified microbes comprise a synergistic effect in the pharmaceutical composition as compared to any of the microbes individually. 
     
     
         36 . The method of  claim 21 , wherein the pharmaceutical composition modulates gut permeability in the subject. 
     
     
         37 . The method of  claim 21 , wherein the population of isolated and purified microbes produce butyrate in the subject. 
     
     
         38 . The method of  claim 21 , further comprising determining a composition of a microbiome of the subject. 
     
     
         39 . The method of  claim 38 , wherein the determining the composition of the microbiome comprises long-read sequencing. 
     
     
         40 . The method of  claim 21 , wherein said treating results in an altered microbiome of the subject.