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Microbiome-encoded bile acid metabolism modulates colonic transit times

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 sc...

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Autores principales: Li, Naisi, Koester, Sean T., Lachance, Daniel M., Dutta, Moumita, Cui, Julia Yue, Dey, Neelendu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188381/
https://www.ncbi.nlm.nih.gov/pubmed/34142026
http://dx.doi.org/10.1016/j.isci.2021.102508
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author Li, Naisi
Koester, Sean T.
Lachance, Daniel M.
Dutta, Moumita
Cui, Julia Yue
Dey, Neelendu
author_facet Li, Naisi
Koester, Sean T.
Lachance, Daniel M.
Dutta, Moumita
Cui, Julia Yue
Dey, Neelendu
author_sort Li, Naisi
collection PubMed
description 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.
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spelling pubmed-81883812021-06-16 Microbiome-encoded bile acid metabolism modulates colonic transit times Li, Naisi Koester, Sean T. Lachance, Daniel M. Dutta, Moumita Cui, Julia Yue Dey, Neelendu iScience Article 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. Elsevier 2021-05-05 /pmc/articles/PMC8188381/ /pubmed/34142026 http://dx.doi.org/10.1016/j.isci.2021.102508 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Li, Naisi
Koester, Sean T.
Lachance, Daniel M.
Dutta, Moumita
Cui, Julia Yue
Dey, Neelendu
Microbiome-encoded bile acid metabolism modulates colonic transit times
title Microbiome-encoded bile acid metabolism modulates colonic transit times
title_full Microbiome-encoded bile acid metabolism modulates colonic transit times
title_fullStr Microbiome-encoded bile acid metabolism modulates colonic transit times
title_full_unstemmed Microbiome-encoded bile acid metabolism modulates colonic transit times
title_short Microbiome-encoded bile acid metabolism modulates colonic transit times
title_sort microbiome-encoded bile acid metabolism modulates colonic transit times
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188381/
https://www.ncbi.nlm.nih.gov/pubmed/34142026
http://dx.doi.org/10.1016/j.isci.2021.102508
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