Jane M. Natividad, Allison Agus, Julien Planchais, Bruno Lamas, Anne Charlotte Jarry, Rebeca Martin, Marie-Laure Michel, Caroline Chong-Nguyen, Ronan Roussel, Marjolene Straube, Sarah Jegou, Claire McQuitty, Maude Le Gall, Gregory da Costa, Emmanuelle Lecornet, Chloé Michaudel, Morgane Modoux, Jeremy Glodt, Chantal Bridonneau, Bruno Sovran, Louise Dupraz, Andre Bado, Mathias L. Richard, Philippe Langella, Boris Hansel, Jean-Marie Launay, Ramnik J. Xavier, Henri Duboc, Harry Sokol
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.