The role of fungi in C. difficile infection: An underappreciated transkingdom interaction

•Fungi are minor constituents of the gut microbiota whose role is not well understood.•Fungal enrichment has been detected in gut microbiota of patients with C. difficile.•In a murine model, introducing C. albicans modulates course of C. difficile infection. Novel culture independent technologies have further elucidated the composition of the human mycobiome, though the role of fungi in human health and disease remains largely unknown. Recent studies have suggested conflicting roles for fungi in the gastrointestinal tract, underscoring the complexity of the interactions between the mycobiome, its bacterial counterpart, and the host. One key example is the observation that fungal taxa are overrepresented in patients with Clostridioides difficile infection (CDI), suggesting a role for fungi in this disease. Recent studies in murine models have demonstrated the ability of the commensal fungus Candida albicans to alter the course of CDI, supporting the notion that fungi play a role in this infection. This review summarizes current data on fungi and CDI, and shows that views of the dysbiotic state that is central to the pathogenesis of CDI are incomplete without consideration of the mycobiome.