Methods and materials for using biomarkers which predict susceptibility to clostridium difficile infection

Abstract

This document relates to biomarkers of gut microbiota dysbiosis. Bacteria that are increased or decreased in gut microbiota dysbiosis can be used as biomarkers to predict dysbiosis in patients with diarrhea and/or to predict susceptibility to Clostridium difficile infection (CDI). In addition, provided herein are compositions including at least three bacteria that are de creased in gut microbiota dysbiosis which can be used, for example, to restore heathy gut microbiota (e.g., by probiotic or by fecal microbiota transplant) to treat CDI.

1 - 8 . (canceled) 
     
     
         9 . A method for treating  C. difficile  infection in a mammal, the method comprising:
 administering to the mammal a composition comprising at least three bacteria that are decreased in gut microbiota dysbiosis;   wherein the at least three bacteria that are decreased in gut microbiota dysbiosis are selected from the group consisting of  Roseburia, Faecalibacterium, Akkermansia, Bacteroides, Blautia,  and  Bacteroides.      
     
     
         10 . The method of  claim 9 , wherein the at least three bacteria that are decreased in gut microbiota dysbiosis comprise  Roseburia feacis, Faecalibacterium prausnitzii,  and  Akkermansia muciniphila.    
     
     
         11 . The method of  claim 9 , wherein the method comprises identifying said mammal as having said  C. difficile  infection prior to said administration. 
     
     
         12 . The method of any of claims  1 ,  5 , or  claim 9 , wherein said mammal is a human. 
     
     
         13 . The method of  claim 12 , wherein said human exhibits at least one clinical biomarker of dysbiosis. 
     
     
         14 . The method of  claim 13 , wherein the at least one clinical biomarker selected from the group consisting of current/recent hospitalization, immune suppression, current/recent antibiotic use, and prior  C. difficile  infection. 
     
     
         15 . A composition comprising at least three bacteria that are decreased in gut microbiota dysbiosis selected from the group consisting of  Roseburia, Faecalibacterium, Akkermansia, Bacteroides, Blautia,  and  Bacteroides.    
     
     
         16 . The composition of  claim 15 , wherein the at least three bacteria that are decreased in gut microbiota dysbiosis comprise  Roseburia feacis, Faecalibacterium prausnitzii,  and  Akkermansia muciniphila.    
     
     
         17 . The composition of  claim 15 , wherein the composition is a pill, tablet, capsule, or enema. 
     
     
         18 . The composition of  claim 15 , wherein the composition is configured to deliver said at least three bacteria to the intestines of said mammal. 
     
     
         19 - 31 . (canceled) 
     
     
         32 . A method for preventing  C. difficile  infection in a mammal, the method comprising:
 administering to the mammal a composition comprising at least three bacteria that are decreased in gut microbiota dysbiosis;   wherein the at least two bacteria that are decreased in gut microbiota dysbiosis are selected from the group consisting of  Roseburia, Faecalibacterium, Akkermansia, Bacteroides, Blautia,  and  Bacteroides.      
     
     
         33 . The method of  claim 32 , wherein the at least two bacteria that are decreased in gut microbiota dysbiosis comprise  Roseburia feacis  and  Faecalibacterium prausnitzii.    
     
     
         34 . The composition of  claim 32 , wherein the composition is administered by fecal microbiota transplant (FMT). 
     
     
         35 . The composition of  claim 32 , wherein the FMT is administered by enema, colonoscope, nasogastric tube, or nasoduodenal tube. 
     
     
         36 . The method of  claim 32 , wherein the method comprises identifying said mammal as having increased susceptibility to  C. difficile  infection prior to said administration. 
     
     
         37 . The method of  claim 32 , wherein the mammal is identified as having increased susceptibility to  C. difficile  infection by determining that said mammal has an increase in the level of at least one free amino acid in a fecal sample obtained from the mammal, wherein the at least one amino acid is selected from the group consisting of proline, alanine, glycine, histidine, isoleucine, leucine, methionine, phenylalanine, threonine, tryptophan, tyrosine, and valine. 
     
     
         38 . The method of  claim 32 , wherein said mammal is a human.