The Bile Acid-Diet-Microbiome Axis in Clostridioides difficile Infection

Clostridioides difficile infection (CDI) remains a major cause of antibiotic-associated diarrhea, with recurrence largely driven by disruption of the gut microbiota and impaired colonization resistance. Bile acids have emerged as key mediators in this process, as primary conjugated bile acids promote C. difficile spore germination, whereas microbiota-derived secondary bile acids can inhibit germination, vegetative growth, and toxin activity. Diet further modulates CDI susceptibility by shaping microbial composition, short-chain fatty acid production, bile acid transformation, epithelial barrier integrity, and intestinal inflammation. Western-style diets, and low fiber intake, may favor dysbiosis and a bile acid profile permissive to CDI, while fiber-rich and Mediterranean-type dietary patterns may support beneficial anaerobes, microbial metabolites, and mucosal resilience. This narrative review summarizes current evidence on the bile acid-diet-microbiome axis in CDI pathogenesis, recurrence, and therapy. It also discusses standard treatment limitations, microbiome-based therapeutics, dietary interventions, and emerging bile acid-targeted strategies. Understanding this axis may support future precision approaches aimed not only at suppressing C. difficile, but also at restoring microbiota function and durable colonization resistance.