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    Mental health profoundly impacts inflammatory responses in the body. This is particularly apparent in inflammatory bowel disease (IBD), in which psychological stress is associated with exacerbated disease flares. Here, we discover a critical role for the enteric nervous system (ENS) in mediating the aggravating effect of chronic stress on intestinal inflammation. We find that chronically elevated levels of glucocorticoids drive the generation of an inflammatory subset of enteric glia that promotes monocyte- and TNF-mediated inflammation via CSF1. Additionally, glucocorticoids cause transcriptional immaturity in enteric neurons, acetylcholine deficiency, and dysmotility via TGF-β2. We verify the connection between the psychological state, intestinal inflammation, and dysmotility in three cohorts of IBD patients. Together, these findings offer a mechanistic explanation for the impact of the brain on peripheral inflammation, define the ENS as a relay between psychological stress and gut inflammation, and suggest that stress management could serve as a valuable component of IBD care. Copyright © 2023 Elsevier Inc. All rights reserved.


    Kai Markus Schneider, Niklas Blank, Yelina Alvarez, Katharina Thum, Patrick Lundgren, Lev Litichevskiy, Madeleine Sleeman, Klaas Bahnsen, Jihee Kim, Simon Kardo, Shaan Patel, Lenka Dohnalová, Giulia T Uhr, Hélène C Descamps, Susanna Kircher, Alana M McSween, Ashkan Rezazadeh Ardabili, Kelsey M Nemec, Monica T Jimenez, Lila G Glotfelty, Joshua D Eisenberg, Emma E Furth, Jorge Henao-Mejia, F Chris Bennett, Marie J Pierik, Mariëlle Romberg-Camps, Zlatan Mujagic, Marco Prinz, Carolin V Schneider, E John Wherry, Meenakshi Bewtra, Robert O Heuckeroth, Maayan Levy, Christoph A Thaiss. The enteric nervous system relays psychological stress to intestinal inflammation. Cell. 2023 Jun 22;186(13):2823-2838.e20

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    PMID: 37236193

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