Gut Microbial Catabolites of Tryptophan Are Ligands and Agonists of the Aryl Hydrocarbon Receptor: A Detailed Characterization
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F20%3A00525016" target="_blank" >RIV/68081707:_____/20:00525016 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15310/20:73601278
Result on the web
<a href="https://apps.webofknowledge.com/full_record.do?product=WOS&search_mode=AdvancedSearch&qid=5&SID=D4vgosHuHfIf388IPgX&page=1&doc=1" target="_blank" >https://apps.webofknowledge.com/full_record.do?product=WOS&search_mode=AdvancedSearch&qid=5&SID=D4vgosHuHfIf388IPgX&page=1&doc=1</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/ijms21072614" target="_blank" >10.3390/ijms21072614</a>
Alternative languages
Result language
angličtina
Original language name
Gut Microbial Catabolites of Tryptophan Are Ligands and Agonists of the Aryl Hydrocarbon Receptor: A Detailed Characterization
Original language description
We examined the effects of gut microbial catabolites of tryptophan on the aryl hydrocarbon receptor (AhR). Using a reporter gene assay, we show that all studied catabolites are low-potency agonists of human AhR. The efficacy of catabolites differed substantially, comprising agonists with no or low (i3-propionate, i3-acetate, i3-lactate, i3-aldehyde), medium (i3-ethanol, i3-acrylate, skatole, tryptamine), and high (indole, i3-acetamide, i3-pyruvate) efficacies. We displayed ligand-selective antagonist activities by i3-pyruvate, i3-aldehyde, indole, skatole, and tryptamine. Ligand binding assay identified low affinity (skatole, i3-pyruvate, and i3-acetamide) and very low affinity (i3-acrylate, i3-ethanol, indole) ligands of the murine AhR. Indole, skatole, tryptamine, i3-pyruvate, i3-acrylate, and i3-acetamide induced CYP1A1 mRNA in intestinal LS180 and HT-29 cells, but not in the AhR-knockout HT-29 variant. We observed a similar CYP1A1 induction pattern in primary human hepatocytes. The most AhR-active catabolites (indole, skatole, tryptamine, i3-pyruvate, i3-acrylate, i3-acetamide) elicited nuclear translocation of the AhR, followed by a formation of AhR-ARNT heterodimer and enhanced binding of the AhR to the CYP1A1 gene promoter. Collectively, we comprehensively characterized the interactions of gut microbial tryptophan catabolites with the AhR, which may expand the current understanding of their potential roles in intestinal health and disease.
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
10608 - Biochemistry and molecular biology
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
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
International Journal of Molecular Sciences
ISSN
1422-0067
e-ISSN
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Volume of the periodical
21
Issue of the periodical within the volume
7
Country of publishing house
CH - SWITZERLAND
Number of pages
17
Pages from-to
2614
UT code for WoS article
000535574200356
EID of the result in the Scopus database
2-s2.0-85083407203