The chemorepellent effect of metformin limits bacterial penetration into mammalian mucus by altering bacterial motility
Year: 2026
Type: preprint
Abstract: Metformin improves metabolic health and remodels the intestinal microbiota, yet how these microbial changes contribute to therapeutic benefits remains incompletely understood. We combined human metagenomics, quantitative analyses of bacterial behavior and ex vivo mucus models to investigate how metformin modulates host–microbiota interactions. Human metagenomics revealed metformin-associated enrichment of chemotaxis- and motility-related genes. At millimolar concentrations, metformin acted as a bacterial chemorepellent, an effect abolished by deletion of the chemotaxis regulator CheY and dependent on the chemoreceptor Tsr. Direct metformin exposure or fecal water from metformin-treated individuals reduced bacterial penetration into mucin, an effect reproduced in intestinal mucus from pigs fed a moderate-fat diet. Metformin treatment was further associated with reduced fecal flagellin activity and increased anti-flagellin IgA. Together, these findings identify bacterial chemotaxis as a target of metformin and reveal a mechanism by which metformin may limit bacterial access to the intestinal mucus barrier.
Institutions: Centre National de la Recherche Scientifique, Inserm, Université Paris Cité, Université Paris Sciences et Lettres, Sorbonne Université, Nutrition et obésité : approches systémiques, Physique et Mécanique des Milieux Hétérogènes, Institut Pasteur, Microbiologie Intégrative et Moléculaire, AgroParisTech, Université Paris-Saclay, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Modélisation Systémique Appliquée aux Ruminants, Pitié-Salpêtrière Hospital, Centre d'Immunologie et des Maladies Infectieuses, Assistance Publique – Hôpitaux de Paris
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: École Normale Supérieure, European Commission, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Fondation pour la Recherche Médicale, Assistance publique-Hôpitaux de Paris, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, H2020 Marie Skłodowska-Curie Actions, HORIZON EUROPE European Innovation Council
Awards: Metabolic diseases from the point of view of the gut bacterial motility and mucus barrier, EMULBIONT: Impact of dietary food additive EMULsifiers on pathoBIONT’s pathogenic potential in chronic inflammatory diseases: from mechanism to prevention, G1190173965, Integrative analysis of the interaction between jejunal microbiota, the host and dietary factors in metabolic diseases, The role of microbiota-derived peptidoglycan in host physiology, Metabolic diseases from the point of view of the gut bacterial motility and mucus barrier, Dynamique de la REsistance aux Antibiotiques dans le Microbiote intestinal humain: combinaison d'une cohorte informée sur nutrition à des études quantitatives sur un modèle in vitro d'intestin, G3458847772, Precision Nutrition to optimize immune response for metabolic health, Microbiota-Additives Interaction Mapping and Mechanisms for Personalized Nutrition in the Healthy and Diseased Populations, G5296751580, G5373655261, Peptidoglycome-based gut microbiome analysis applied to Juvenile Idiopathic Arthritis., Microswimmers in complex environments, G7525143621, G7713766279, Analysis of the interplay between digestive microbiota and immune system in the development of rheumatoid arthritis
OpenAlex ID: W7213632834