PUBLICATION
Fxr signaling and microbial metabolism of bile salts in the zebrafish intestine
- Authors
- Wen, J., Mercado, G.P., Volland, A., Doden, H.L., Lickwar, C.R., Crooks, T., Kakiyama, G., Kelly, C., Cocchiaro, J.L., Ridlon, J.M., Rawls, J.F.
- ID
- ZDB-PUB-210728-13
- Date
- 2021
- Source
- Science advances 7(30): (Journal)
- Registered Authors
- Lickwar, Colin, Mercado, Gilberto Padilla, Rawls, John F.
- Keywords
- none
- Datasets
- GEO:GSE173570
- MeSH Terms
-
- Animals
- Bile Acids and Salts*/metabolism
- Intestines
- Liver/metabolism
- Mammals/metabolism
- Receptors, Cytoplasmic and Nuclear/genetics
- Receptors, Cytoplasmic and Nuclear/metabolism
- Transcription Factors/metabolism
- Zebrafish*/metabolism
- PubMed
- 34301599 Full text @ Sci Adv
Citation
Wen, J., Mercado, G.P., Volland, A., Doden, H.L., Lickwar, C.R., Crooks, T., Kakiyama, G., Kelly, C., Cocchiaro, J.L., Ridlon, J.M., Rawls, J.F. (2021) Fxr signaling and microbial metabolism of bile salts in the zebrafish intestine. Science advances. 7(30).
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping