The enteric nervous system relays psychological stress to intestinal inflammation

Kai Markus Schneider; Niklas Blank; Yelina Alvarez; Katharina Thum; Patrick Lundgren; Lev Litichevskiy; Madeleine Sleeman; Klaas Bahnsen; Jihee Kim; Simon Kardo; Shaan Patel; Lenka Dohnalova; Giulia T. Uhr; Helene 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; Marielle Romberg-Camps; Zlatan Mujagic; Marco Prinz; Carolin V. Schneider; E. John Wherry; Meenakshi Bewtra; Robert O. Heuckeroth; Maayan Levy; Christoph A. Thaiss

doi:10.1016/j.cell.2023.05.001

The enteric nervous system relays psychological stress to intestinal inflammation

Kai Markus Schneider, Niklas Blank, Yelina Alvarez, Katharina Thum, Patrick Lundgren, Lev Litichevskiy, Madeleine Sleeman, Klaas Bahnsen, Jihee Kim, Simon Kardo, Shaan Patel, Lenka Dohnalova, Giulia T. Uhr, Helene C. Descamps, Susanna Kircher, Alana M. McSween, Ashkan Rezazadeh Ardabili, Kelsey M. Nemec, Monica T. Jimenez, Lila G. GlotfeltyJoshua D. Eisenberg, Emma E. Furth, Jorge Henao-Mejia, F. Chris Bennett, Marie J. Pierik, Marielle Romberg-Camps, Zlatan Mujagic, Marco Prinz, Carolin V. Schneider, E. John Wherry, Meenakshi Bewtra, Robert O. Heuckeroth, Maayan Levy^*, Christoph A. Thaiss^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	2823-2838.e20
Number of pages	37
Journal	Cell
Volume	186
Issue number	13
DOIs	https://doi.org/10.1016/j.cell.2023.05.001
Publication status	Published - 22 Jun 2023

Keywords

COLITIS
SEVERITY
EXPOSURE
PATHWAY
CELLS
AXIS

Access to Document

10.1016/j.cell.2023.05.001

Cite this

Schneider, K. M., Blank, N., Alvarez, Y., Thum, K., Lundgren, P., Litichevskiy, L., Sleeman, M., Bahnsen, K., Kim, J., Kardo, S., Patel, S., Dohnalova, L., Uhr, G. T., Descamps, H. C., Kircher, S., McSween, A. M., Ardabili, A. R., Nemec, K. M., Jimenez, M. T., ... Thaiss, C. A. (2023). The enteric nervous system relays psychological stress to intestinal inflammation. Cell, 186(13), 2823-2838.e20. https://doi.org/10.1016/j.cell.2023.05.001

@article{23e3030b7fa54b159126203181e9909d,

title = "The enteric nervous system relays psychological stress to intestinal inflammation",

abstract = "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.",

keywords = "COLITIS, SEVERITY, EXPOSURE, PATHWAY, CELLS, AXIS",

author = "Schneider, {Kai Markus} and Niklas Blank and Yelina Alvarez and Katharina Thum and Patrick Lundgren and Lev Litichevskiy and Madeleine Sleeman and Klaas Bahnsen and Jihee Kim and Simon Kardo and Shaan Patel and Lenka Dohnalova and Uhr, {Giulia T.} and Descamps, {Helene C.} and Susanna Kircher and McSween, {Alana M.} and Ardabili, {Ashkan Rezazadeh} and Nemec, {Kelsey M.} and Jimenez, {Monica T.} and Glotfelty, {Lila G.} and Eisenberg, {Joshua D.} and Furth, {Emma E.} and Jorge Henao-Mejia and Bennett, {F. Chris} and Pierik, {Marie J.} and Marielle Romberg-Camps and Zlatan Mujagic and Marco Prinz and Schneider, {Carolin V.} and Wherry, {E. John} and Meenakshi Bewtra and Heuckeroth, {Robert O.} and Maayan Levy and Thaiss, {Christoph A.}",

year = "2023",

month = jun,

day = "22",

doi = "10.1016/j.cell.2023.05.001",

language = "English",

volume = "186",

pages = "2823--2838.e20",

journal = "Cell",

issn = "0092-8674",

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Schneider, KM, Blank, N, Alvarez, Y, Thum, K, Lundgren, P, Litichevskiy, L, Sleeman, M, Bahnsen, K, Kim, J, Kardo, S, Patel, S, Dohnalova, L, Uhr, GT, Descamps, HC, Kircher, S, McSween, AM, Ardabili, AR, Nemec, KM, Jimenez, MT, Glotfelty, LG, Eisenberg, JD, Furth, EE, Henao-Mejia, J, Bennett, FC, Pierik, MJ, Romberg-Camps, M, Mujagic, Z, Prinz, M, Schneider, CV, Wherry, EJ, Bewtra, M, Heuckeroth, RO, Levy, M & Thaiss, CA 2023, 'The enteric nervous system relays psychological stress to intestinal inflammation', Cell, vol. 186, no. 13, pp. 2823-2838.e20. https://doi.org/10.1016/j.cell.2023.05.001

TY - JOUR

T1 - The enteric nervous system relays psychological stress to intestinal inflammation

AU - Schneider, Kai Markus

AU - Blank, Niklas

AU - Alvarez, Yelina

AU - Thum, Katharina

AU - Lundgren, Patrick

AU - Litichevskiy, Lev

AU - Sleeman, Madeleine

AU - Bahnsen, Klaas

AU - Kim, Jihee

AU - Kardo, Simon

AU - Patel, Shaan

AU - Dohnalova, Lenka

AU - Uhr, Giulia T.

AU - Descamps, Helene C.

AU - Kircher, Susanna

AU - McSween, Alana M.

AU - Ardabili, Ashkan Rezazadeh

AU - Nemec, Kelsey M.

AU - Jimenez, Monica T.

AU - Glotfelty, Lila G.

AU - Eisenberg, Joshua D.

AU - Furth, Emma E.

AU - Henao-Mejia, Jorge

AU - Bennett, F. Chris

AU - Pierik, Marie J.

AU - Romberg-Camps, Marielle

AU - Mujagic, Zlatan

AU - Prinz, Marco

AU - Schneider, Carolin V.

AU - Wherry, E. John

AU - Bewtra, Meenakshi

AU - Heuckeroth, Robert O.

AU - Levy, Maayan

AU - Thaiss, Christoph A.

PY - 2023/6/22

Y1 - 2023/6/22

N2 - 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.

AB - 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.

KW - COLITIS

KW - SEVERITY

KW - EXPOSURE

KW - PATHWAY

KW - CELLS

KW - AXIS

U2 - 10.1016/j.cell.2023.05.001

DO - 10.1016/j.cell.2023.05.001

M3 - Article

C2 - 37236193

SN - 0092-8674

VL - 186

SP - 2823-2838.e20

JO - Cell

JF - Cell

IS - 13

ER -