Ecological drivers of Clostridioides difficile disease severity

Clostridioides difficile infection (CDI) is a common cause of antibiotic-associated diarrhea and arises from disruption of the resident microbiota in the gastrointestinal tract. Despite being a major cause of morbidity and mortality worldwide, CDI presents as a wide spectrum of clinical manifestations, ranging from completely asymptomatic infection to severe and fulminant colitis. Recent research has revealed that CDI disease severity is influenced by the complex ecosystem of the gut, involving interactions between C. difficile, the host, and the resident gut microbiota. This review will summarize the current state of the field in understanding how the balance of interactions in the gut alters CDI disease severity using clinical data and mouse models of infection. In addition, external factors influencing these interactions, such as diet and pharmaceutical drugs, will be discussed. Ultimately, a comprehensive understanding of the ecological factors influencing patient outcome will be critical for the design of novel therapeutics for primary and recurrent CDI.