Impaired aryl hydrocarbon receptor ligand production by the gut microbiota is a key factor in metabolic syndrome
Open accessAbstract
The extent to which microbiota alterations define or influence the outcome of metabolic diseases is still unclear, but the byproducts of microbiota metabolism are known to have an important role in mediating the host-microbiota interaction. Here, we identify that in both pre-clinical and clinical settings, metabolic syndrome is associated with the reduced capacity of the microbiota to metabolize tryptophan into derivatives that are able to activate the aryl hydrocarbon receptor. This alteration is not merely an effect of the disease as supplementation with AhR agonist or a Lactobacillus strain, with a high AhR ligand-production capacity, leads to improvement of both dietary- and genetic-induced metabolic impairments, particularly glucose dysmetabolism and liver steatosis, through improvement of intestinal barrier function and secretion of the incretin hormone GLP-1. These results highlight the role of gut microbiota-derived metabolites as a biomarker and as a basis for novel preventative or therapeutic interventions for metabolic disorders.
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Dietary supplementation with synthetic AhR agonists or bacterial strains that naturally produce AhR ligands by tryptophan metabolism enhanced gut barrier function via secretion of incretin hormone glucagon-like peptide-1.
“Dietary supplementation with synthetic AhR agonists or bacterial strains that naturally produce AhR ligands by Tryptophan metabolism enhanced gut barrier function via secretion of incretin hormone glucagon-like peptide-1.95”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [95]
An impaired capacity of gut microbiota to metabolize tryptophan into multiple AhR agonists has been associated with metabolic syndrome in humans and mice.
“An impaired capacity of gut microbiota to metabolize tryptophan into multiple AhR agonists has been associated with metabolic syndrome in humans and mice.95”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [95]
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- Authors
- Natividad, J. M., Agus, A., Planchais, J., Lamas, B., Jarry, A. C., Martin, R., Michel, M.-L., Chong-Nguyen, C., Roussel, R., Straube, M., Jegou, S., McQuitty, C., Le Gall, M., da Costa, G., Lecornet, E., Michaudel, C., Modoux, M., Glodt, J., Bridonneau, C., Sovran, B., Dupraz, L., Bado, A., Richard, M. L., Langella, P., Hansel, B., Launay, J.-M., Xavier, R. J., Duboc, H., & Sokol, H.
- Affiliations
- AgroParisTech (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Broad Institute (US)
- Corresponding author
- Sokol, Harry
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2018-11
- Volume
- 28
- Issue
- 5
- Pages
- 737-749.e4
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2883853179
- Cited by
- 642
- References
- 45
- Citations by year
- 2026: 80 · 2025: 81 · 2024: 95 · 2023: 101 · 2022: 99 · 2021: 78 · 2020: 67 · 2019: 33 · 2018: 6
- FWCI
- 16.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- European Research Council (ERC-2016-StG-71577)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- aryl hydrocarbon receptor, gut microbiota, tryptophan metabolism, AhR agonists, Lactobacillus, metabolic syndrome, hepatic steatosis, intestinal barrier function, glucagon-like peptide-1, host-microbiota interactions, gut microbiota metabolites, biomarkers
- MeSH terms
- Gastrointestinal Microbiome, Animals, Ligands, Male, Mice, Inbred C57BL, Tryptophan, Receptors, Aryl Hydrocarbon, Probiotics, Metabolic Syndrome, Mice, Limosilactobacillus reuteri
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