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

Jia Wen, Gilberto Padilla Mercado, Alyssa Volland, Heidi L. Doden, Colin R. Lickwar, Taylor Crooks, Genta Kakiyama, Cecelia Kelly, Jordan L. Cocchiaro, Jason M. Ridlon, John F. Rawls

Research output: Contribution to journalArticlepeer-review


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 C27 bile alcohol and a C24 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.

Original languageEnglish (US)
Article numbereabg1371
JournalScience Advances
Issue number30
StatePublished - Jul 2021

ASJC Scopus subject areas

  • General


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