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Gut microbiota-produced succinate promotes C. difficile infection after antibiotic treatment or motility disturbance.


ABSTRACT: Clostridium difficile is a leading cause of antibiotic-associated diarrhea. The mechanisms underlying C. difficile expansion after microbiota disturbance are just emerging. We assessed the gene expression profile of C. difficile within the intestine of gnotobiotic mice to identify genes regulated in response to either dietary or microbiota compositional changes. In the presence of the gut symbiont Bacteroides thetaiotaomicron, C. difficile induces a pathway that metabolizes the microbiota fermentation end-product succinate to butyrate. The low concentration of succinate present in the microbiota of conventional mice is transiently elevated upon antibiotic treatment or chemically induced intestinal motility disturbance, and C. difficile exploits this succinate spike to expand in the perturbed intestine. A C. difficile mutant compromised in succinate utilization is at a competitive disadvantage during these perturbations. Understanding the metabolic mechanisms involved in microbiota-C. difficile interactions may help to identify approaches for the treatment and prevention of C. difficile-associated diseases.

SUBMITTER: Ferreyra JA 

PROVIDER: S-EPMC4859344 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Gut microbiota-produced succinate promotes C. difficile infection after antibiotic treatment or motility disturbance.

Ferreyra Jessica A JA   Wu Katherine J KJ   Hryckowian Andrew J AJ   Bouley Donna M DM   Weimer Bart C BC   Sonnenburg Justin L JL  

Cell host & microbe 20141201 6


Clostridium difficile is a leading cause of antibiotic-associated diarrhea. The mechanisms underlying C. difficile expansion after microbiota disturbance are just emerging. We assessed the gene expression profile of C. difficile within the intestine of gnotobiotic mice to identify genes regulated in response to either dietary or microbiota compositional changes. In the presence of the gut symbiont Bacteroides thetaiotaomicron, C. difficile induces a pathway that metabolizes the microbiota fermen  ...[more]

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