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.

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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