Interaction between the intestinal microbiota and host in Clostridium difficile colonization resistance

Abstract

Clostridium difficile infection (CDI) has become one of the most prevalent and costly nosocomial infections. In spite of the importance of CDI, our knowledge of the pathogenesis of this infection is still rudimentary. Although previous use of antibiotics is generally considered to be the sine qua non of CDI, the mechanisms by which antibiotics render the host susceptible to C. difficile are not well defined. In this review, we will explore what is known about how the indigenous microbiota acts in concert with the host to prevent colonization and virulence of C. difficile and how antibiotic administration disturbs host-microbiota homeostasis, leading to CDI.

Figure 1

Potential mechanisms by which the indigenous microbiota can mediate colonization resistance against C. difficile. Specific members of the microbiome can either directly, or indirectly interfere with the proliferation of C. difficile within the gut. Direct inhibition can occur via competition for nutrients, the conversion of nutrients or host metabolites to compounds that are inhibitory to C. difficile or by the production of primary microbial products that inhibit C. difficile. Indirect control of C. difficile can occur via interactions between the indigenous microbiota and the host that results in the expression of host products that control C. difficile colonization and proliferation. Detection of microbial-associated molecular patterns (MAMPs) can trigger the host immune signaling cascades leading to the production of innate (e.g. antimicrobial peptides) or adaptive (e.g. IgA) immune effectors. Abbreviations: SCFA, short-chain fatty acids.

Figure 2

Bile acid metabolism and C. difficile. Conjugated bile salts produced by the liver are metabolized in the intestine, primarily by activities carried out by members of the gut microbiota. Primary bile salts as well as their metabolites can have direct effects on C. difficile, primarily affecting germination of spores as well as the activity of vegetative cells. The balance of the positive and negative effects on C. difficile, which in turn reflect the overall community structure of the gut microbiota, may determine the ultimate clinical outcome of C. difficile exposure.