Clostridioides difficile–Restrictive and –Permissive Gut Microbiomes: A Review

Clostridioides difficile infections (CDI) are common healthcare-associated infections in the United States and constitute a significant clinical and economic burden. A critical risk factor for developing CDI is gut microbiota dysbiosis. In this review, we summarize the determinants and consequences of C. difficile–restrictive and –permissive gut microbiomes, as well as therapeutic options that aim to stabilize GI consortia. The gut microbiome is a consortium of organisms (bacteria, fungi, archaea, viruses), as well as their genetically associated material and activities. Taken together, this “eubiosis” helps regulate host functions such as immune response(s) and gut barrier function, and also provides necessary metabolites for host health. Diversity of the microbiome is also associated with colonization resistance against pathogens, notably C. difficile. The microbiome shift from eubiosis to dysbiosis is a hallmark preceding CDI, as well as subsequent recurrent infections. Restoring the microbiome to eubiosis is the focus of several CDI treatment strategies. Targeting key microbiota and metabolite shifts conducive to a C. difficile–restrictive microbiome is crucial for treating primary, as well as recurrent CDI.