MICROBIOME-ENCODED BILE ACID METABOLISM MODULATES COLONIC TRANSIT TIMES

Microbiome-encoded bile acid metabolism modulates colonic transit times

Microbiome-encoded bile acid metabolism modulates colonic transit times

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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 Spatula 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 Horse Stall Guards diet ingredient, evidencing exquisite sensitivity of the ENS to environmental perturbations.

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