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
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
35533897
DOI
10.1016/j.jnutbio.2022.109042
PII: S0955-2863(22)00113-9
Knihovny.cz E-zdroje
- Klíčová slova
- Aryl hydrocarbon receptor, Butyrate, Cytochromes P450, Drug metabolism, gut-liver axis,
- MeSH
- butyráty * metabolismus farmakologie MeSH
- játra metabolismus MeSH
- kolon metabolismus MeSH
- kyseliny mastné těkavé metabolismus MeSH
- lidé MeSH
- receptory aromatických uhlovodíků genetika metabolismus MeSH
- střevní mikroflóra * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- butyráty * MeSH
- kyseliny mastné těkavé MeSH
- receptory aromatických uhlovodíků MeSH
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.
Citace poskytuje Crossref.org
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