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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 120; no. 4; p. e2209936120
• Main Authors: Wheeler, Richard, Bastos, Paulo André Dias, Disson, Olivier, Rifflet, Aline, Gabanyi, Ilana, Spielbauer, Julia, Bérard, Marion, Lecuit, Marc, Boneca, Ivo Gomperts
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 24-01-2023
• Subjects: Acetylcholine receptors (muscarinic); Animal biology; Animals; Bacteria - metabolism; Bacteriology; Biochemistry, Molecular Biology; Biological Sciences; Cell Wall - metabolism; Cell walls; Cellular Biology; Digestive system; Gastrointestinal tract; Intestine; Life Sciences; Mammals - metabolism; Microbiology and Parasitology; Microbiota; Molecular biology; Parasympathetic nervous system; Peptidoglycan - metabolism; Peptidoglycans; Physiological effects; Polymers; Subcellular Processes; Translocation; Tropism; peptidoglycan; gut microbiota; systemic trafficking
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2209936120

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.