Microbiome-encoded bile acid metabolism modulates colonic transit times

Summary Gut motility is regulated by the microbiome via mechanisms that include bile acid metabolism. To localize the effects of microbiome-generated bile acids, we colonized gnotobiotic mice with different synthetic gut bacterial communities that were metabolically phenotyped using a functional in vitro screen. Using two different marker-based assays of gut transit, we inferred that bile acids exert effects on colonic transit. We validated this using an intra-colonic bile acid infusion assay and determined that these effects were dependent upon signaling via the bile acid receptor, TGR5. The intra-colonic bile acid infusion experiments further revealed sex-biased bile acid-specific effects on colonic transit, with lithocholic acid having the largest pro-motility effect. Transcriptional responses of the enteric nervous system (ENS) were stereotypic, regional, and observed in response to different microbiota, their associated bile acid profiles, and even to a single diet ingredient, evidencing exquisite sensitivity of the ENS to environmental perturbations.
Graphical abstract
Highlights • Gut microbiome-generated bile acids regulate colonic transit via TGR5. • Lithocholic acid had the largest colonic pro-motility effect. • Bile acids exert sex-biased effects on gut transit times. • Enteric nervous system transcriptional responses are regional and microbiome-specific.
Microbiology; Microbiome; Gastroenterology