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

Cell Host Microbe. 2014 Dec 10;16(6):770-7. doi: 10.1016/j.chom.2014.11.003.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Bacteroides / physiology
  • Clostridium Infections / drug therapy*
  • Clostridium Infections / metabolism
  • Clostridium Infections / microbiology
  • Clostridium difficile / drug effects
  • Clostridium difficile / physiology*
  • Female
  • Gastrointestinal Tract / metabolism
  • Gastrointestinal Tract / microbiology*
  • Host-Pathogen Interactions
  • Humans
  • Male
  • Mice
  • Microbiota*
  • Succinic Acid / metabolism*

Substances

  • Anti-Bacterial Agents
  • Succinic Acid