Establishment and characterization of stable, diverse, fecal-derived in vitro microbial communities that model the intestinal microbiota

Abstract

Efforts to probe the role of the gut microbiota in disease would benefit from a system in which patient-derived bacterial communities can be studied at scale. We addressed this by validating a strategy to propagate phylogenetically complex, diverse, stable, and highly reproducible stool-derived communities invitro. We generated hundreds of invitro communities cultured from diverse stool samples in various media; certain media generally preserved inoculum composition, and inocula from different subjects yielded source-specific community compositions. Upon colonization of germ-free mice, community composition was maintained, and the host proteome resembled the host from which the community was derived. Treatment with ciprofloxacin invivo increased susceptibility to Salmonella invasion invitro, and the invitro response to ciprofloxacin was predictive of compositional changes observed invivo, including the resilience and sensitivity of each Bacteroides species. These findings demonstrate that stool-derived invitro communities can serve as a powerful system for microbiota research.