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Published on: May 2, 2018
Microbiota-induced active translocation of peptidoglycan across the intestinal barrier dictates its within-host
Richard Wheeler1, Paulo André Dias Bastos1, Olivier Disson2
1Institut Pasteur, Université Paris Cité, CNRS Unité Mixe de Recherche 6047, INSERM U1306, Unité de Biologie et génétique de la paroi bactérienne F-75015, Paris, France.
Abstract:
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.
Insights
Bacterial peptidoglycan absorption from the gut actively transports to host organs, especially the brain. This process is regulated by the gut microbiota and the parasympathetic nervous system.
Area of Science:
- Microbiology
- Immunology
- Neuroscience
Background:
- Peptidoglycan is a major bacterial cell wall component.
- Its translocation from the gut to host tissues influences host physiology and behavior.
- The mechanisms and regulation of this gut barrier translocation are not well understood.
Purpose of the Study:
- To characterize the absorption and systemic dissemination of peptidoglycan across the intestinal barrier.
- To elucidate the regulatory pathways involved in peptidoglycan translocation.
- To understand the uptake of microbiota-derived molecular signals.
Main Methods:
- In vivo studies to track peptidoglycan absorption and distribution.
- Investigation of microbiota-induced processes.
- Analysis of the parasympathetic pathway and muscarinic acetylcholine receptor involvement.
Main Results:
- Peptidoglycan exhibits specific organotropism upon gut absorption, with a notable preference for the brain.
- Intestinal translocation of peptidoglycan is an active, microbiota-dependent process.
- The parasympathetic pathway, mediated by muscarinic acetylcholine receptors, regulates this translocation.
Conclusions:
- This study reveals key aspects of peptidoglycan absorption and systemic spread from the gut.
- It highlights the role of the microbiota and the nervous system in mediating the host response to bacterial components.
- Fundamental parameters of microbiota molecular signal uptake from the gut are elucidated.
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