Gut Microbial Catabolites of Tryptophan Are Ligands and Agonists of the Aryl Hydrocarbon Receptor: A Detailed Characterization
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 (...
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MDPI AG
2020-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/7/2614 |
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| author | Barbora Vyhlídalová Kristýna Krasulová Petra Pečinková Adéla Marcalíková Radim Vrzal Lenka Zemánková Jan Vančo Zdeněk Trávníček Jan Vondráček Martina Karasová Sridhar Mani Zdeněk Dvořák |
| author_facet | Barbora Vyhlídalová Kristýna Krasulová Petra Pečinková Adéla Marcalíková Radim Vrzal Lenka Zemánková Jan Vančo Zdeněk Trávníček Jan Vondráček Martina Karasová Sridhar Mani Zdeněk Dvořák |
| author_sort | Barbora Vyhlídalová |
| collection | DOAJ |
| 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 <i>CYP1A1</i> 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. |
| first_indexed | 2024-03-10T20:34:28Z |
| format | Article |
| id | doaj.art-04270e0b74804ce4a71a903df1898c26 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T20:34:28Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-04270e0b74804ce4a71a903df1898c262023-11-19T21:08:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01217261410.3390/ijms21072614Gut Microbial Catabolites of Tryptophan Are Ligands and Agonists of the Aryl Hydrocarbon Receptor: A Detailed CharacterizationBarbora Vyhlídalová0Kristýna Krasulová1Petra Pečinková2Adéla Marcalíková3Radim Vrzal4Lenka Zemánková5Jan Vančo6Zdeněk Trávníček7Jan Vondráček8Martina Karasová9Sridhar Mani10Zdeněk Dvořák11Department of Cell Biology and Genetics, Faculty of Science, Palacky University, Slechtitelu 27, 783 71 Olomouc, Czech RepublicDepartment of Cell Biology and Genetics, Faculty of Science, Palacky University, Slechtitelu 27, 783 71 Olomouc, Czech RepublicDepartment of Cell Biology and Genetics, Faculty of Science, Palacky University, Slechtitelu 27, 783 71 Olomouc, Czech RepublicDepartment of Cell Biology and Genetics, Faculty of Science, Palacky University, Slechtitelu 27, 783 71 Olomouc, Czech RepublicDepartment of Cell Biology and Genetics, Faculty of Science, Palacky University, Slechtitelu 27, 783 71 Olomouc, Czech RepublicDepartment of Cell Biology and Genetics, Faculty of Science, Palacky University, Slechtitelu 27, 783 71 Olomouc, Czech RepublicDivision of Biologically Active Complexes and Molecular Magnets, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University, Šlechtitelů 27, 783 71 Olomouc, Czech RepublicDivision of Biologically Active Complexes and Molecular Magnets, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University, Šlechtitelů 27, 783 71 Olomouc, Czech RepublicDepartment of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 61265 Brno, Czech RepublicDepartment of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 61265 Brno, Czech RepublicDepartment of Genetics and Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Cell Biology and Genetics, Faculty of Science, Palacky University, Slechtitelu 27, 783 71 Olomouc, Czech RepublicWe 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 <i>CYP1A1</i> 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.https://www.mdpi.com/1422-0067/21/7/2614aryl hydrocarbon receptortryptophanindolesmicrobiome |
| spellingShingle | Barbora Vyhlídalová Kristýna Krasulová Petra Pečinková Adéla Marcalíková Radim Vrzal Lenka Zemánková Jan Vančo Zdeněk Trávníček Jan Vondráček Martina Karasová Sridhar Mani Zdeněk Dvořák Gut Microbial Catabolites of Tryptophan Are Ligands and Agonists of the Aryl Hydrocarbon Receptor: A Detailed Characterization International Journal of Molecular Sciences aryl hydrocarbon receptor tryptophan indoles microbiome |
| title | Gut Microbial Catabolites of Tryptophan Are Ligands and Agonists of the Aryl Hydrocarbon Receptor: A Detailed Characterization |
| title_full | Gut Microbial Catabolites of Tryptophan Are Ligands and Agonists of the Aryl Hydrocarbon Receptor: A Detailed Characterization |
| title_fullStr | Gut Microbial Catabolites of Tryptophan Are Ligands and Agonists of the Aryl Hydrocarbon Receptor: A Detailed Characterization |
| title_full_unstemmed | Gut Microbial Catabolites of Tryptophan Are Ligands and Agonists of the Aryl Hydrocarbon Receptor: A Detailed Characterization |
| title_short | Gut Microbial Catabolites of Tryptophan Are Ligands and Agonists of the Aryl Hydrocarbon Receptor: A Detailed Characterization |
| title_sort | gut microbial catabolites of tryptophan are ligands and agonists of the aryl hydrocarbon receptor a detailed characterization |
| topic | aryl hydrocarbon receptor tryptophan indoles microbiome |
| url | https://www.mdpi.com/1422-0067/21/7/2614 |
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