Microbe-microbe interactions during Clostridioides difficile infection

Abstract

Clostridioides difficile is the leading cause of hospital-acquired gastrointestinal infections and a major public health burden in the United States. C. difficile infection causes a spectrum of disease from mild diarrhea to severe complications such as pseudomembranous colitis, toxic megacolon and death. This broad range of disease is only partially explained by bacterial genetic factors, host genetics, comorbidities and previous drug exposures. Another important factor is the gut microbiome, the disruption of which results in a loss of colonization resistance to C. difficile. Here, we review how gut microbiota and their metabolites impact C. difficile virulence and influence disease.

Figure 1:. Impact of Gut Microbiota and Intestinal Metabolites on C. difficile Infection

Exposure to C. difficile can cause a spectrum of disease ranging from asymptomatic colonization to mild infection treatable with antibiotics to severe intestinal pathologies. A disturbed gut microbiota usually precedes C. difficile infection as the normal enteric microbial flora provide colonization resistance against the pathogen. This is accomplished by their conversion of primary bile acids to secondary bile acids, which generally inhibit the growth of C. difficile. In contrast, other bacterial metabolic products, such as sialic acid and succinate, promote C. difficile growth. Intestinal epithelial cells and resident innate immune cells are affected by C. difficile toxin, which ultimately leads to disruption of the epithelial layer and development of a pro-inflammatory environment. Several other metabolites and bacteria are under consideration for their role in C. difficile disease (discussed in the text) by either directly impacting the pathogen or indirectly influencing the host immune response to infection.