Microbiota-induced active translocation of peptidoglycan across the intestinal barrier dictates its within-host dissemination

Richard Wheeler (1) , Paulo André Dias Bastos (1) , Olivier Disson (2) , Aline Rifflet (1) , Ilana Gabanyi (3, 4) , Julia Spielbauer (1) , Marion Bérard (5) , Marc Lecuit (2, 6, 7, 8) , Ivo Gomperts Boneca (1)

1 Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall
2 Biologie des Infections - Biology of Infection
3 Perception et Mémoire / Perception and Memory
4 Microenvironnement et Immunité - Microenvironment and Immunity
5 C2RA - Animalerie Centrale (plateforme) - Central Animal Facility (platform)
6 CNRL - Centre National de Référence Listeria - National Reference Center Listeria
7 CC-OMS / WHO-CC - Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria
8 CHU Necker - Enfants Malades [AP-HP]

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.

Keywords: gut microbiota; peptidoglycan; systemic trafficking

Domains: Life Sciences [q-bio]; Microbiology and Parasitology; Bacteriology; Life Sciences [q-bio]; Animal biology; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Molecular biology; Life Sciences [q-bio]; Cellular Biology; Subcellular Processes [q-bio.SC]

Richard Wheeler, Paulo André Dias Bastos, Olivier Disson, Aline Rifflet, Ilana Gabanyi, et al.. Microbiota-induced active translocation of peptidoglycan across the intestinal barrier dictates its within-host dissemination. Proceedings of the National Academy of Sciences of the United States of America, 2023, 120 (4), pp.e2209936120. ⟨10.1073/pnas.2209936120⟩. ⟨pasteur-03995078⟩