Antimicrobial Use, Human Gut Microbiota and Clostridium difficile Colonization and Infection

Caroline Vincent, Amee R Manges, Caroline Vincent, Amee R Manges

Abstract

Clostridium difficile infection (CDI) is the most important cause of nosocomial diarrhea. Broad-spectrum antimicrobials have profound detrimental effects on the structure and diversity of the indigenous intestinal microbiota. These alterations often impair colonization resistance, allowing the establishment and proliferation of C. difficile in the gut. Studies involving animal models have begun to decipher the precise mechanisms by which the intestinal microbiota mediates colonization resistance against C. difficile and numerous investigations have described gut microbiota alterations associated with C. difficile colonization or infection in human subjects. Fecal microbiota transplantation (FMT) is a highly effective approach for the treatment of recurrent CDI that allows the restoration of a healthy intestinal ecosystem via infusion of fecal material from a healthy donor. The recovery of the intestinal microbiota after FMT has been examined in a few reports and work is being done to develop custom bacterial community preparations that could be used as a replacement for fecal material.

Keywords: Clostridium difficile infection; antimicrobials; colonization resistance; fecal microbiota transplantation; intestinal microbiota.

Figures

Figure 1
Figure 1
Metabolism of bile acids and their impact on the germination and growth of C. difficile. Primary bile acids are synthesized by the liver and excreted in the gastrointestinal tract but the majority are reabsorbed in the distal ileum and returned to the liver via enterohepatic circulation. The fraction of bile acids that escapes enterohepatic circulation passes into the colon where they are metabolized and transformed into secondary bile acids by the gut microbiota. Bile acids and their metabolites can either inhibit or enhance the germination of spores, as well as the growth of vegetative C. difficile. The overall proportions of bile acids may determine the clinical outcome of C. difficile infection. Figure adapted from [45].

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