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Fxr signaling and microbial metabolism of bile salts in the zebrafish intestine

Bile salt synthesis, secretion into the intestinal lumen, and resorption in the ileum occur in all vertebrate classes. In mammals, bile salt composition is determined by host and microbial enzymes, affecting signaling through the bile salt–binding transcription factor farnesoid X receptor (Fxr). How...

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Autores principales: Wen, Jia, Mercado, Gilberto Padilla, Volland, Alyssa, Doden, Heidi L., Lickwar, Colin R., Crooks, Taylor, Kakiyama, Genta, Kelly, Cecelia, Cocchiaro, Jordan L., Ridlon, Jason M., Rawls, John F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302129/
https://www.ncbi.nlm.nih.gov/pubmed/34301599
http://dx.doi.org/10.1126/sciadv.abg1371
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author Wen, Jia
Mercado, Gilberto Padilla
Volland, Alyssa
Doden, Heidi L.
Lickwar, Colin R.
Crooks, Taylor
Kakiyama, Genta
Kelly, Cecelia
Cocchiaro, Jordan L.
Ridlon, Jason M.
Rawls, John F.
author_facet Wen, Jia
Mercado, Gilberto Padilla
Volland, Alyssa
Doden, Heidi L.
Lickwar, Colin R.
Crooks, Taylor
Kakiyama, Genta
Kelly, Cecelia
Cocchiaro, Jordan L.
Ridlon, Jason M.
Rawls, John F.
author_sort Wen, Jia
collection PubMed
description Bile salt synthesis, secretion into the intestinal lumen, and resorption in the ileum occur in all vertebrate classes. In mammals, bile salt composition is determined by host and microbial enzymes, affecting signaling through the bile salt–binding transcription factor farnesoid X receptor (Fxr). However, these processes in other vertebrate classes remain poorly understood. We show that key components of hepatic bile salt synthesis and ileal transport pathways are conserved and under control of Fxr in zebrafish. Zebrafish bile salts consist primarily of a C(27) bile alcohol and a C(24) bile acid that undergo multiple microbial modifications including bile acid deconjugation that augments Fxr activity. Using single-cell RNA sequencing, we provide a cellular atlas of the zebrafish intestinal epithelium and uncover roles for Fxr in transcriptional and differentiation programs in ileal and other cell types. These results establish zebrafish as a nonmammalian vertebrate model for studying bile salt metabolism and Fxr signaling.
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spelling pubmed-83021292021-08-06 Fxr signaling and microbial metabolism of bile salts in the zebrafish intestine Wen, Jia Mercado, Gilberto Padilla Volland, Alyssa Doden, Heidi L. Lickwar, Colin R. Crooks, Taylor Kakiyama, Genta Kelly, Cecelia Cocchiaro, Jordan L. Ridlon, Jason M. Rawls, John F. Sci Adv Research Articles Bile salt synthesis, secretion into the intestinal lumen, and resorption in the ileum occur in all vertebrate classes. In mammals, bile salt composition is determined by host and microbial enzymes, affecting signaling through the bile salt–binding transcription factor farnesoid X receptor (Fxr). However, these processes in other vertebrate classes remain poorly understood. We show that key components of hepatic bile salt synthesis and ileal transport pathways are conserved and under control of Fxr in zebrafish. Zebrafish bile salts consist primarily of a C(27) bile alcohol and a C(24) bile acid that undergo multiple microbial modifications including bile acid deconjugation that augments Fxr activity. Using single-cell RNA sequencing, we provide a cellular atlas of the zebrafish intestinal epithelium and uncover roles for Fxr in transcriptional and differentiation programs in ileal and other cell types. These results establish zebrafish as a nonmammalian vertebrate model for studying bile salt metabolism and Fxr signaling. American Association for the Advancement of Science 2021-07-23 /pmc/articles/PMC8302129/ /pubmed/34301599 http://dx.doi.org/10.1126/sciadv.abg1371 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Wen, Jia
Mercado, Gilberto Padilla
Volland, Alyssa
Doden, Heidi L.
Lickwar, Colin R.
Crooks, Taylor
Kakiyama, Genta
Kelly, Cecelia
Cocchiaro, Jordan L.
Ridlon, Jason M.
Rawls, John F.
Fxr signaling and microbial metabolism of bile salts in the zebrafish intestine
title Fxr signaling and microbial metabolism of bile salts in the zebrafish intestine
title_full Fxr signaling and microbial metabolism of bile salts in the zebrafish intestine
title_fullStr Fxr signaling and microbial metabolism of bile salts in the zebrafish intestine
title_full_unstemmed Fxr signaling and microbial metabolism of bile salts in the zebrafish intestine
title_short Fxr signaling and microbial metabolism of bile salts in the zebrafish intestine
title_sort fxr signaling and microbial metabolism of bile salts in the zebrafish intestine
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302129/
https://www.ncbi.nlm.nih.gov/pubmed/34301599
http://dx.doi.org/10.1126/sciadv.abg1371
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