Higher order metabolic interactions in colonization resistance against Clostridioides difficile

Commensal gut microbiota is fundamental to resisting pathogenic invasion. A notable case is the success of faecal microbiota transplantation in treating recurrent Clostridioides difficile infections. Yet, characteristics of a community that can confer colonisation resistance, and the underlying mechanisms remain largely unknown. Here we use a synthetic community of 14 commensal gut bacteria to uncover inter-species interactions and metabolic pathways underpinning the emergent resilience against pathogen invasion. We challenged this synthetic community, as well as more complex, faecal-matter-derived, communities, with antibiotic treatment and C. difficile in a continues flow bioreactor.