Butyrate acts through HDAC inhibition to enhance aryl hydrocarbon receptor activation by gut microbiota-derived ligands
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F22%3A73613390" target="_blank" >RIV/61989592:15310/22:73613390 - isvavai.cz</a>
Result on the web
<a href="https://www.tandfonline.com/doi/pdf/10.1080/19490976.2022.2105637" target="_blank" >https://www.tandfonline.com/doi/pdf/10.1080/19490976.2022.2105637</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1080/19490976.2022.2105637" target="_blank" >10.1080/19490976.2022.2105637</a>
Alternative languages
Result language
angličtina
Original language name
Butyrate acts through HDAC inhibition to enhance aryl hydrocarbon receptor activation by gut microbiota-derived ligands
Original language description
Aryl hydrocarbon receptor (AhR) is a critical player in the crosstalk between the gut microbiota and its host. However, factors regulating AhR within the gut, which is a complex metabolomic environment, are poorly understood. This study investigates the effect of a combination of metabolites on the activation mechanism of AhR. AhR activity was evaluated using both a luciferase reporter system and mRNA levels of AhR target genes on human cell lines and human colonic explants. AhR activation was studied by radioligand-binding assay, nuclear translocation of AhR by immuofluorescence and protein co-immunoprecipitation of AhR with ARNT. Indirect activation of AhR was evaluated using several tests and inhibitors. The promoter of the target gene CYP1A1 was studied both by chromatin immunoprecipitation and by using an histone deacetylase HDAC inhibitor (iHDAC). Short-chain fatty acids, and butyrate in particular, enhance AhR activity mediated by endogenous tryptophan metabolites without binding to the receptor. This effect was confirmed in human intestinal explants and did not rely on activation of receptors targeted by SCFAs, inhibition of AhR degradation or clearance of its ligands. Butyrate acted directly on AhR target gene promoter to reshape chromatin through iHDAC activity. Our findings revealed that butyrate is not an AhR ligand but acts as iHDAC leading to an increase recruitment of AhR to the target gene promoter in the presence of tryptophan-derived AhR agonists. These data contribute to a novel understanding of the complex regulation of AhR activation by gut microbiota-derived metabolites.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30219 - Gastroenterology and hepatology
Result continuities
Project
<a href="/en/project/GA20-00449S" target="_blank" >GA20-00449S: Microbial catabolites of tryptophan as modulators of intestinal health via aryl hydrocarbon receptor</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Gut Microbes
ISSN
1949-0976
e-ISSN
1949-0984
Volume of the periodical
14
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
15
Pages from-to
"2105637-1"-"2105637-15"
UT code for WoS article
000831002100001
EID of the result in the Scopus database
2-s2.0-85135076434