ArticleCell2023
The enteric nervous system relays psychological stress to intestinal inflammation.
Open access · greenAbstract read
In one paragraph
Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
179citing papers in PubMed, 2 pooled it
80.4field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
179 citing papers in PubMed, 2 syntheses or guidelines pooled it, 286 citations in OpenAlex.
- Large-scale multi-trait genome-wide analysis for inflammatory bowel disease reveals new insights into its molecular mechanisms and emphasizes the roles of systemic immune regulation.Briefings in bioinformatics · 2025Pooled it
- Exploring Electrical Neuromodulation as an Alternative Therapeutic Approach in Inflammatory Bowel Diseases.Medicina (Kaunas, Lithuania) · 2024Pooled it
- Review
- Balancing inflammation under stress: glucocorticoid regulation of innate immune pathways.Bioscience reports · 2026Review
- Beyond tumor tracing: physiological uptake of sympathetic ganglia on somatostatin receptor PET/CT - prevalence, patterns, and biological rationale.European journal of nuclear medicine and molecular imaging · 2026Article
- Blocking the mCellular & molecular immunology · 2026Article
- Transcriptome changes of disinhibited somatostatin neurons in the medial prefrontal cortex mediating male-specific stress resilience.Research square · 2026Article
- Neuroimmune interactions: from molecular mechanisms to therapeutic targets.Molecular biomedicine · 2026Review
- Treating the Whole Disease: A Call for Holistic Care for Patients with Inflammatory Bowel Disease.Digestive diseases and sciences · 2026Article
- Psychological adaptation and health-related quality of life in inflammatory bowel disease: a 5-year follow-up study.Research in psychotherapy (Milano) · 2026Article
- Temporal Trends and Socio-Demographic Disparities in Inflammatory Bowel Disease: Insights from the Global Burden of Disease Study 2021.Digestive diseases and sciences · 2026Article
- Blunted Cortisol Awakening Response in Patients with Inflammatory Bowel Disease: A Cross-Sectional Case-Control Study.Medical sciences (Basel, Switzerland) · 2026Article
- Advancing Predictive Modeling of Inflammatory Bowel Disease (IBD) Flares: A Data-Driven Approach Using Lifestyle and Psychosocial Factors from a Remote Monitoring Platform.Digestive diseases and sciences · 2026Observational
- Oral probiotic delivery-based therapeutic strategies for inflammatory bowel disease.Asian journal of pharmaceutical sciences · 2026Review
- Amifostine alleviates ionizing radiation-induced small intestinal motility dysfunction in mice by remodeling the structure of the enteric nervous system.Histochemistry and cell biology · 2026Article
- Crosstalk Between Gut Microbiota, Epigenome, and Neurotransmitters in Health and Disease.Cells · 2026Review
- Stress and the Immune System: Insights From Psychoneuroimmunology.Physiological research · 2026Review
- Chronic stress unleashes an intratumor phage-fibroblast-B cell circuit to promote tumor growth.Cancer cell · 2026Article
- Stress-induced glucocorticoid signaling impairs enteric neurotrophin BDNF-TrkB pathway and drives gastrointestinal dysmotility.The Journal of biological chemistry · 2026Article
- Cortisol Stress Response is Associated with Iron Status in Pregnancy.medRxiv : the preprint server for health sciences · 2026Article
119 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
- Commented on by
- Commented on by
Authors and funding
34 authors at 6 institutions in 3 countries.
Kai Markus SchneiderDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Niklas BlankDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
Yelina AlvarezDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Katharina ThumDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Patrick LundgrenDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Lev LitichevskiyDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Madeleine SleemanDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Klaas BahnsenDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jihee KimDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Simon KardoDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Shaan PatelDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Lenka DohnalováDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Giulia T UhrDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Hélène C DescampsDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Susanna KircherDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Alana M McSweenDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ashkan Rezazadeh ArdabiliDepartment of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands; School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands.
Kelsey M NemecDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Monica T JimenezDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Lila G GlotfeltyDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Joshua D EisenbergDepartment of Pediatrics, Children's Hospital of Philadelphia Research Institute, and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Emma E FurthDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jorge Henao-MejiaDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Protective Immunity, Department of Pathology and Laboratory Medicine, Children's Hospital of Pennsylvania, University of Pennsylvania, Philadelphia, PA 19104, USA.
F Chris BennettDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Marie J PierikDepartment of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands; School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands.
Mariëlle Romberg-CampsDepartment of Gastroenterology, Geriatrics, Internal and Intensive Care Medicine (Co-MIK), Zuyderland Medical Centre, Sittard-Geleen, the Netherlands.
Zlatan MujagicDepartment of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands; School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands.
Marco PrinzInstitute of Neuropathology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, 79104 Freiburg, Germany; Center for Basics in NeuroModulation, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.
Carolin V SchneiderInstitute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
E John WherryInstitute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA; Immune Health, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Meenakshi BewtraDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Robert O HeuckerothDepartment of Pediatrics, Children's Hospital of Philadelphia Research Institute, and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Maayan LevyDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: maayanle@pennmedicine.upenn.edu.
Christoph A ThaissDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: thaiss@pennmedicine.upenn.edu.
University of Pennsylvania · USChildren's Hospital of Philadelphia · USMaastricht University Medical Centre · NLTranslational Therapeutics (United States) · USUniversity of Freiburg · DEZuyderland Medisch Centrum · NL
Funding
VIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Patrick Seale · 1986 to 2026
$48.3MVirology CoreU19AI082630 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG, GEORG Michael LAUER · 2009 to 2026
$48.1MTranslational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Trevor M Penning · 2006 to 2026
$35.3MTRANSGENIC AND CHIMERIC MOUSE COREP30DK050306 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI REBECCA G WELLS · 1997 to 2026
$32.5MSynergies among inhibitory receptors in tolerance, cancer & antiviral immunityP01AI108545 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Dario AA Vignali · 2015 to 2026
$30.8MSequencing and Viral Evolution CoreU19AI117950 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI WHERRY, E. JOHN · 2015 to 2019
$12.0MRadiation and checkpoint blockade for cancer immune therapyP01CA210944 · NCI · UNIVERSITY OF PENNSYLVANIA · PI MAITY, AMIT, MINN, ANDY J · 2017 to 2022
$11.5MBiochemical and cellular mechanisms linking actin mutations to visceral myopathyR01DK128282 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI HEUCKEROTH, ROBERT O · 2021 to 2025
$3.5MVMD-PhD Training in Infectious Disease-Related ResearchT32AI070077 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Michael Lee Atchison · 2008 to 2026
$3.5MTesting the role of BATF as a pioneer transcription factor in effector T cellsR01AI115712 · NIAID · DANA-FARBER CANCER INST · PI KADOCH, CIGALL, WHERRY, E. JOHN · 2015 to 2019
$2.9MMolecular and Functional Analysis of Hirschsprung Defects in Humans and MouseR01DK122798 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ALBERS, KATHRYN MARIE, DAVIS, BRIAN M · 2020 to 2023
$2.8MTemporal control of differentiation and epigenetics of Exhausted CD8 T cells by ToxR01AI155577 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI WHERRY, E. JOHN · 2020 to 2024
$2.7MNCI NIH HHS P01 CA210944NHLBI NIH HHS F31 HL160065NIAID NIH HHS P01 AI108545NIAID NIH HHS R01 AI115712NIAID NIH HHS R01 AI155577NIAID NIH HHS T32 AI070077NIAID NIH HHS T32 AI141393NIAID NIH HHS U19 AI082630NIAID NIH HHS U19 AI117950NIA NIH HHS DP2 AG067492NIA NIH HHS DP2 AG067511NIDDK NIH HHS P30 DK019525NIDDK NIH HHS P30 DK050306NIDDK NIH HHS R01 DK122798NIDDK NIH HHS R01 DK128282NIDDK NIH HHS R01 DK129691NIDDK NIH HHS T32 DK101371NIEHS NIH HHS P30 ES013508NINDS NIH HHS R21 NS116574
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.
Indexed as
Enteric Nervous SystemInflammatory Bowel DiseasesGlucocorticoidsHumansInflammationStress, PsychologicalGlucocorticoidsenteric gliaenteric nervous systementeric neuronsglucocorticoidsIBDmonocytesneuro-immune interactionspsychological stress
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.