Identification of Clostridioides difficile-Inhibiting Gut Commensals Using Culturomics, Phenotyping, and Combinatorial Community Assembly

Antibiotic treatment causes instability of gut microbiota and the loss of colonization resistance, thus allowing pathogens such as Clostridioides difficile to colonize and causing recurrent infection and mortality. Although fecal microbiome transplantation has been shown to be an effective treatment for C. difficile infection (CDI), a more desirable approach would be the use of a defined mix of inhibitory gut bacteria. The C. difficile -inhibiting species and bacterial combinations identified herein improve the understanding of the ecological interactions controlling colonization resistance against C. difficile and could aid in the design of defined bacteriotherapy as a nonantibiotic alternative against CDI.