Butyrate, a typical product of gut microbiome, affects function of the AhR gene, being a possible agent of crosstalk between gut microbiome, and hepatic drug metabolism.

Autor: Jourova L; Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic. Electronic address: lenka.jourova@upol.cz., Anzenbacherova E; Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic., Dostal Z; Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic., Anzenbacher P; Department of Pharmacology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic., Briolotti P; IRMB, University Montpellier, INSERM, CHU Montpellier, Montpellier, France., Rigal E; IRMB, University Montpellier, INSERM, CHU Montpellier, Montpellier, France., Daujat-Chavanieu M; IRMB, University Montpellier, INSERM, CHU Montpellier, Montpellier, France. Electronic address: martine.daujat@inserm.fr., Gerbal-Chaloin S; IRMB, University Montpellier, INSERM, CHU Montpellier, Montpellier, France.
Jazyk: angličtina
Zdroj: The Journal of nutritional biochemistry [J Nutr Biochem] 2022 Sep; Vol. 107, pp. 109042. Date of Electronic Publication: 2022 May 07.
DOI: 10.1016/j.jnutbio.2022.109042
Abstrakt: Modulation of gut microbiome composition seems to be a promising therapeutic strategy for a wide range of pathologic states. However, these microbiota-targeted interventions may affect production of microbial metabolites, circulating factors in the gut-liver axis influencing hepatic drug metabolism with possible clinical relevance. Butyrate, a short-chain fatty acid produced through microbial fermentation of dietary fibers in the colon, has well established anti-inflammatory role in the intestine, while the effect of butyrate on the liver is unknown. In this study, we have evaluated the effect of butyrate on hepatic AhR activity and AhR-regulated gene expression. We have showed that AhR and its target genes were upregulated by butyrate in dose-dependent manner in HepG2-C3 as well as in primary human hepatocytes. The involvement of AhR has been proved using specific AhR antagonists and siRNA-mediated AhR silencing. Experiments with AhR reporter cells have shown that butyrate regulates the expression of AhR target genes by modulating the AhR activity. Our results suggest also epigenetic action by butyrate on AhR and its repressor (AHRR) presumably through mechanisms based on HDAC inhibition in the liver. Our results demonstrate that butyrate may influence the drug-metabolizing ability of liver enzymes e.g., through the interaction with AhR-dependent pathways.
(Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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