Microbial and metabolic interactions between the gastrointestinal tract and Clostridium difficile infection

Abstract

Antibiotics disturb the gastrointestinal tract microbiota and in turn reduce colonization resistance against Clostridium difficile. The mechanism for this loss of colonization resistance is still unknown but likely reflects structural (microbial) and functional (metabolic) changes to the gastrointestinal tract. Members of the gut microbial community shape intestinal metabolism that provides nutrients and ultimately supports host immunity. This review will discuss how antibiotics alter the structure of the gut microbiota and how this impacts bacterial metabolism in the gut. It will also explore the chemical requirements for C. difficile germination, growth, toxin production and sporulation. Many of the metabolites that influence C. difficile physiology are products of gut microbial metabolism including bile acids, carbohydrates and amino acids. To restore colonization resistance against C. difficile after antibiotics a targeted approach restoring both the structure and function of the gastrointestinal tract is needed.

Keywords: Clostridium difficile; antibiotics; colonization resistance; gut metabolome; gut microbiota.

Figure 1. Functional role of the indigenous gastrointestinal tract microbiota. The gastrointestinal tract microbiota provides many metabolic functions that are able to convert luminal compounds into secondary metabolites. The chemical reactions (labeled in red) can produce metabolites that are both beneficial and harmful to the host. Fluorescence in situ hybridization (FISH) of the gastrointestinal tract microbiota in a wild type mouse is at the center (red, hybridized with Cy3-labeled Eub338) and was provided by Christine Bassis, PhD.