ArticleJournal of proteome research2019
Microbiota Metabolism Promotes Synthesis of the Human Ah Receptor Agonist 2,8-Dihydroxyquinoline.
Article in Journal of proteome research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- 2,8-Dihydroxyquinoline ameliorates oligoasthenozoospermia by inhibiting MAPK14-mediated spermatogonial ferroptosis.Molecular biology reports · 2026Article
- Activity-guided substructure prioritization accelerates discovery of gut microbiota-derived immune-regulating metabolites.Nature communications · 2026Article
- Circadian tryptophan metabolism contributes to systemic aryl hydrocarbon receptor activity.iScience · 2026Article
- The aryl hydrocarbon receptor: structure, signaling, physiology and pathology.Signal transduction and targeted therapy · 2026Review
- A taxon-specific measurement of disruption in a multi-modal study of microbiomes and metabolomes reveals system-wide dysbiosis preceding HIV-1 infection.Nature communications · 2025Article
- Microbiome and metabolome changes in laying hens induced by dietary epsilon-polylysine.Poultry science · 2025Article
- Safety and effects of acetylated and butyrylated high-amylose maize starch on youths recently diagnosed with type 1 diabetes: A pilot study.Diabetes, obesity & metabolism · 2025Article
- Safety and effects of acetylated and butyrylated high amylose maize starch in recently diagnosed youths with type 1 diabetes; a Pilot Study.medRxiv : the preprint server for health sciences · 2024Article
- Molecular networking identifies an AHR-modulating benzothiazole from white button mushrooms (Journal of functional foods · 2023Article
- Activation of the aryl hydrocarbon receptor in inflammatory bowel disease: insights from gut microbiota.Frontiers in cellular and infection microbiology · 2023Review
- Review
- Untargeted fecal metabolome analysis in obese dogs after weight loss achieved by feeding a high-fiber-high-protein diet.Metabolomics : Official journal of the Metabolomic Society · 2021Article
- How Ah Receptor Ligand Specificity Became Important in Understanding Its Physiological Function.International journal of molecular sciences · 2020Review
- Article
- The Aryl Hydrocarbon Receptor (AHR) as a Potential Target for the Control of Intestinal Inflammation: Insights from an Immune and Bacteria Sensor Receptor.Clinical reviews in allergy & immunology · 2020Review
- The aryl hydrocarbon receptor as a mediator of host-microbiota interplay.Gut microbes · 2020Review
- Intestinal microbiota-derived tryptophan metabolites are predictive of Ah receptor activity.Gut microbes · 2020Article
- Dysregulated bile acid receptor-mediated signaling and IL-17A induction are implicated in diet-associated hepatic health and cognitive function.Biomarker research · 2020Article
- Reversal of obesity and liver steatosis in mice via inhibition of aryl hydrocarbon receptor and altered gene expression of CYP1B1, PPARα, SCD1, and osteopontin.International journal of obesity (2005) · 2020Article
- Microbiome is a functional modifier of P450 drug metabolism.Current pharmacology reports · 2019Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
The aryl hydrocarbon receptor (AHR) is a major regulator of immune function within the gastrointestinal tract. Resident microbiota are capable of influencing AHR-dependent signaling pathways via production of an array of bioactive molecules that act as AHR agonists, such as indole or indole-3-aldehyde. Bacteria produce a number of quinoline derivatives, of which some function as quorum-sensing molecules. Thus, we screened relevant hydroxyquinoline derivatives for AHR activity using AHR responsive reporter cell lines. 2,8-Dihydroxyquinoline (2,8-DHQ) was identified as a species-specific AHR agonist that exhibits full AHR agonist activity in human cell lines, but only induces modest AHR activity in mouse cells. Additional dihydroxylated quinolines tested failed to activate the human AHR. Nanomolar concentrations of 2,8-DHQ significantly induced CYP1A1 expression and, upon cotreatment with cytokines, synergistically induced IL6 expression. Ligand binding competition studies subsequently confirmed 2,8-DHQ to be a human AHR ligand. Several dihydroxyquinolines were detected in human fecal samples, with concentrations of 2,8-DHQ ranging between 0 and 3.4 pmol/mg feces. Additionally, in mice the microbiota was necessary for the presence of DHQ in cecal contents. These results suggest that microbiota-derived 2,8-DHQ would contribute to AHR activation in the human gut, and thus participate in the protective and homeostatic effects observed with gastrointestinal AHR activation.
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