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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F22%3A73614961" target="_blank" >RIV/61989592:15110/22:73614961 - isvavai.cz</a>

Výsledek na webu

<a href="https://reader.elsevier.com/reader/sd/pii/S0955286322001139?token=043F05965D78FC9DE8B7DB5874F2BB4D07D70C131CFA168C2667A0E2CDCA059830AD72751A4D157537D479FF50BA7331&originRegion=eu-west-1&originCreation=20221220185342" target="_blank" >https://reader.elsevier.com/reader/sd/pii/S0955286322001139?token=043F05965D78FC9DE8B7DB5874F2BB4D07D70C131CFA168C2667A0E2CDCA059830AD72751A4D157537D479FF50BA7331&originRegion=eu-west-1&originCreation=20221220185342</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jnutbio.2022.109042" target="_blank" >10.1016/j.jnutbio.2022.109042</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

JOURNAL OF NUTRITIONAL BIOCHEMISTRY

ISSN

0955-2863

e-ISSN

1873-4847

Svazek periodika

107

Číslo periodika v rámci svazku

Sep

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

"109042(1)"-"109042(10)"

Kód UT WoS článku

000806731000002

EID výsledku v databázi Scopus

2-s2.0-85130826255