Host and microbial-derived metabolites for Clostridioides difficile infection: Contributions, mechanisms and potential applications

Clostridioides difficile infection (CDI), which mostly occurs in hospitalized patients, is the most common and costly health care-associated disease. However, the biology of C. difficile remains incompletely understood. Current therapeutics are still challenged by the frequent recurrence of CDI. Advances in metabolomics facilitate our understanding of the etiology of CDI, which is not merely an alteration in the structure of the gut microbial community but also a dysbiosis metabolic setting promoting the germination, expansion and virulence of C. difficile. Therefore, we summarized the gut microbial and metabolic profiles for CDI under different conditions, such as those of postantibiotic treatment and postfecal microbiota transplantation. The current understanding of the role of host and gut microbial-derived metabolites as well as other nutrients in preventing or alleviating the disease symptoms of CDI will also be provided in this review. We hope that a specific nutrient-centric dietary strategy or the administration of certain nutrients to the colon could serve as an alternate line of investigation for the prophylaxis and mitigation of CDI in the future. Nevertheless, rigorously designed basic studies and randomized controlled trials need to be conducted to assess the functional mechanisms and effects of such therapeutics.