Identification of the novel role of butyrate as AhR ligand in human intestinal epithelial cells.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
24 01 2019
24 01 2019
Historique:
received:
26
06
2018
accepted:
28
11
2018
entrez:
26
1
2019
pubmed:
27
1
2019
medline:
8
8
2020
Statut:
epublish
Résumé
The ligand activated transcription factor, aryl hydrocarbon receptor (AhR) emerged as a critical regulator of immune and metabolic processes in the gastrointestinal tract. In the gut, a main source of AhR ligands derives from commensal bacteria. However, many of the reported microbiota-derived ligands have been restricted to indolyl metabolites. Here, by screening commensal bacteria supernatants on an AhR reporter system expressed in human intestinal epithelial cell line (IEC), we found that the short chain fatty acid (SCFA) butyrate induced AhR activity and the transcription of AhR-dependent genes in IECs. We showed that AhR ligand antagonists reduced the effects of butyrate on IEC suggesting that butyrate could act as a ligand of AhR, which was supported by the nuclear translocation of AhR induced by butyrate and in silico structural modelling. In conclusion, our findings suggest that (i) butyrate activates AhR pathway and AhR-dependent genes in human intestinal epithelial cell-lines (ii) butyrate is a potential ligand for AhR which is an original mechanism of gene regulation by SCFA.
Identifiants
pubmed: 30679727
doi: 10.1038/s41598-018-37019-2
pii: 10.1038/s41598-018-37019-2
pmc: PMC6345974
doi:
Substances chimiques
Butyrates
0
Ligands
0
Receptors, Aryl Hydrocarbon
0
Receptors, G-Protein-Coupled
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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