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Article Dans Une Revue Brain, Behavior, and Immunity Année : 2024

Bacterial peptidoglycan serves as a critical modulator of the gut-immune-brain axis in Drosophila

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Metabolites and compounds derived from gut-associated bacteria can modulate numerous physiological processes in the host, including immunity and behavior. Using a model of oral bacterial infection, we previously demonstrated that gut-derived peptidoglycan (PGN), an essential constituent of the bacterial cell envelope, influences female fruit fly egg-laying behavior by activating the NF-κB cascade in a subset of brain neurons. These findings underscore PGN as a potential mediator of communication between gut bacteria and the brain in Drosophila, prompting further investigation into its impact on all brain cells. Through high-resolution mass spectrometry, we now show that PGN fragments produced by gut bacteria can rapidly reach the central nervous system. In Addition, by employing a combination of whole-genome transcriptome analyses, comprehensive genetic assays, and reporter gene systems, we reveal that gut bacterial infection triggers a PGN dose-dependent NF-κB immune response in perineurial glia, forming the continuous outer cell layer of the blood–brain barrier. Furthermore, we demonstrate that persistent PGN-dependent NF-κB activation in perineurial glial cells correlates with a reduction in lifespan and early neurological decline. Overall, our findings establish gut-derived PGN as a critical mediator of the gut-immune-brain axis in Drosophila.
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pasteur-04614803 , version 1 (17-06-2024)

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Florent Fioriti, Aline Rifflet, Ivo Gomperts Boneca, Olivier Zugasti, Julien Royet. Bacterial peptidoglycan serves as a critical modulator of the gut-immune-brain axis in Drosophila. Brain, Behavior, and Immunity, 2024, 119, pp.878 - 897. ⟨10.1016/j.bbi.2024.05.009⟩. ⟨pasteur-04614803⟩
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