Compositions and methods for characterizing and restoring gastrointestinal, skin, and nasal microbiota

Abstract

The present invention relates to characterizing changes in mammalian bacterial gastrointestinal, cutaneous and nasal microbiota associated with antibiotic treatment and various disease conditions (such as asthma, allergy, obesity, metabolic syndrome, gastrointestinal reflux disease (GERD), eosinophilic esophagitis, gastro-esophageal junction adenocarcinomas (GEJAC), infections due to bacteria that are resistant to antibiotics, including Methicillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile, vancomycin-resistant enterococci, etc.) and related diagnostic and therapeutic methods. Therapeutic methods of the invention involve the use of live bacterial inoculants that are capable of restoring healthy mammalian bacterial gastrointestinal, skin, and nasal microbiota.

1 . A method of treating a disease in a mammal comprising administering to the mammal a therapeutically effective amount of a probiotic composition comprising one or more bacterial strains, wherein the composition (i) stimulates growth and/or activity of bacteria which are under-represented in microbiota of the mammal as compared to healthy subjects and/or (ii) inhibits growth and/or activity of bacteria which are over-represented in microbiota of the mammal as compared to healthy subjects. 
     
     
         2 - 23 . (canceled) 
     
     
         24 . The method of  claim 29 , wherein the prebiotic and/or probiotic composition lowers the relative abundance of genes encoding an enzyme involved in metabolism or regulation of metabolism of the short chain fatty acid (SCFA) in the microbiota of the mammal. 
     
     
         25 . A method for treating obesity and related disorders in a mammal in need thereof comprising administering to the mammal a therapeutically effective amount of a prebiotic and/or probiotic composition which alters gastrointestinal microbiota of the mammal to lower the level of gastric inhibitory polypeptide (GIP) in the serum of the mammal. 
     
     
         26 . (canceled) 
     
     
         27 . A method for diagnosing obesity and related disorders in a mammal comprising comparing the total number of Butyryl CoA transferase (BCoAT)—encoding genes in gastrointestinal microbiota of the mammal and in healthy control gastrointestinal microbiota, wherein the increased levels of BCoAT genes are indicative of the disorder. 
     
     
         28 . (canceled) 
     
     
         29 . A method for treating obesity and related disorders in a mammal in need thereof comprising administering to the mammal a therapeutically effective amount of a prebiotic and/or probiotic composition which composition inhibits metabolism of a short chain fatty acid (SCFA) in a microbiota of the mammal. 
     
     
         30 . The method of  claim 29 , wherein the prebiotic and/or probiotic composition inhibits butyrate and/or acetate and/or propionate metabolism in the microbiota of the mammal. 
     
     
         31 . The method of  claim 30 , wherein the prebiotic and/or probiotic composition inhibits an enzyme involved in butyrate and/or acetate and/or propionate synthesis in the microbiota of the mammal. 
     
     
         32 . The method of  claim 31 , wherein the prebiotic and/or probiotic composition inhibits a Butyryl CoA transferase (BCoAT) enzyme or phosphotrans-butyrylase/butyrate kinase enzyme in the microbiota of the mammal. 
     
     
         33 . The method of  claim 31 , wherein the prebiotic and/or probiotic composition inhibits an Acetate CoA transferase (AcCoAT) enzyme or phosphotransacetylase/acetate kinase enzyme in the microbiota of the mammal. 
     
     
         34 . The method of  claim 29 , wherein the microbiota is a gastrointestinal microbiota. 
     
     
         35 . The method of  claim 29 , wherein an obesity-related disorder is metabolic syndrome, diabetes, insulin-deficiency related disorder, insulin-resistance related disorder, ischemia, oxidative stress, atherosclerosis, hypertension, or abnormal lipid metabolism. 
     
     
         36 . The method of  claim 24 , wherein the enzyme involved in metabolism of the short chain fatty acid (SCFA) is involved in butyrate and/or acetate and/or propionate synthesis in the microbiota of the mammal. 
     
     
         37 . The method of  claim 36 , wherein the enzyme involved in butyrate synthesis is a Butyryl CoA transferase (BCoAT) enzyme or phosphotrans-butyrylase/butyrate kinase enzyme. 
     
     
         38 . The method of  claim 36 , wherein the enzyme involved in acetate synthesis is an Acetate CoA transferase (AcCoAT) enzyme or phosphotransacetylase/acetate kinase enzyme. 
     
     
         39 . The method of  claim 24 , wherein the mammal has an increased relative abundance of genes encoding the enzyme involved in metabolism or regulation of metabolism of the short chain fatty acid (SCFA) as compared to a healthy control microbiota. 
     
     
         40 . The method of  claim 39 , wherein the control is microbiota from one or more non-obese age- and gender-matched healthy mammals of the same species. 
     
     
         41 . The method of  claim 24 , wherein the method further comprises determining the relative abundance of genes encoding the enzyme involved in metabolism or regulation of metabolism of the short chain fatty acid (SCFA) in the microbiota of the mammal before and/or after the administration of the prebiotic and/or probiotic composition. 
     
     
         42 . The method of  claim 41 , wherein the relative abundance of genes is determined using PCR, high throughput sequencing or metagenomics. 
     
     
         43 . The method of  claim 29 , wherein the prebiotic and/or probiotic composition is administered orally, rectally or by enema. 
     
     
         44 . The method of  claim 29 , wherein the mammal is human. 
     
     
         45 . The method of  claims 29 , wherein the mammal is a child.