1. Microbiota-induced active translocation of peptidoglycan across the intestinal barrier dictates its within-host dissemination
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Richard Wheeler, Paulo André Dias Bastos, Olivier Disson, Aline Rifflet, Ilana Gabanyi, Julia Spielbauer, Marion Bérard, Marc Lecuit, Ivo Gomperts Boneca, Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall, Institut Pasteur [Paris] (IP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Perception et Mémoire / Perception and Memory, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Microenvironnement et Immunité - Microenvironment and Immunity, Animalerie Centrale (plateforme) - Central Animal Facility (platform) (C2RA), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre National de Référence Listeria - National Reference Center Listeria (CNR), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This project has received funding from the Institut Carnot Pasteur Microbes & Santé, and the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no 665807. A.R. and I.G.B. laboratory were supported by Investissement d’Avenir program, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10-LABX-62-IBEID). I.G.B. laboratory was also supported by the Investissement d’Avenir program (RHU Torino Lumière ANR-16-RHUS-0008), by the French National Research Agency (ANR-16-CE15-0021) and by R&D grants from Danone and MEIJI. Additional funding was provided by DIM1Health., We thank the UTechS PBI, a member of the France–BioImaging infrastructure network supported by the French National Research Agency (ANR-10–INSB–04, Investments for the future) for microscope usage and assistance. We thank the members of the Centre for Gnotobiology Platform of the Institut Pasteur (especially Thierry Angélique, Eddie Maranghi, Martine Jacob, and Marisa Gabriela Lopez Dieguez), and of the Institut Pasteur Central Animal Facility for all their assistance with animal studies. P.A.D.B. was part of the Pasteur-Paris University International PhD Program., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-16-RHUS-0008,LUMIERE,LUMIERE(2016), ANR-16-CE15-0021,PG-Brain,Modulation de l'activité du cerveau par le peptidoglycan bactérien(2016), and European Project: 665807,H2020,H2020-MSCA-COFUND-2014,PASTEURDOC(2015)
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Multidisciplinary ,gut microbiota ,systemic trafficking ,[SDV.BA]Life Sciences [q-bio]/Animal biology ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,peptidoglycan ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology - Abstract
International audience; Peptidoglycan, the major structural polymer forming the cell wall of bacteria, is an important mediator of physiological and behavioral effects in mammalian hosts. These effects are frequently linked to its translocation from the intestinal lumen to host tissues. However, the modality and regulation of this translocation across the gut barrier has not been precisely addressed. In this study, we characterized the absorption of peptidoglycan across the intestine and its systemic dissemination. We report that peptidoglycan has a distinct tropism for host organs when absorbed via the gut, most notably by favoring access to the brain. We demonstrate that intestinal translocation of peptidoglycan occurs through a microbiota-induced active process. This process is regulated by the parasympathetic pathway via the muscarinic acetylcholine receptors. Together, this study reveals fundamental parameters concerning the uptake of a major microbiota molecular signal from the steady-state gut.
- Published
- 2023
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