Environmental stress–induced gastrointestinal permeability is mediated by endogenous glucocorticoids in the rat
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Background & aims Abnormal presentation of luminal constituents to the mucosal immune system, caused by dysfunction of the intestinal epithelial barrier, is a candidate theory for the cause of Crohn's disease. Increased epithelial permeability is found in subgroups of patients at high risk for the development of Crohn's disease and has been found to precede disease recurrence. Clinical observations have suggested that disease recurrence can follow times of increased psychological stress, although the underlying mechanism remains obscure. We hypothesized that environmental stress increases gastrointestinal permeability. Methods We evaluated site-specific gastrointestinal permeability after application of graded levels of stress in rats. Results Increased epithelial permeability after stress was shown in all regions of the gastrointestinal tract and seemed to be mediated by adrenal corticosteroids. Stress-induced increases in epithelial permeability disappeared after adrenalectomy or pharmacologic blockade of glucocorticoid receptors. Dexamethasone treatment of control animals increased gastrointestinal permeability and mimicked the effects of stress. Conclusions Psychological stress may increase gastrointestinal permeability, allowing luminal constituents access to the mucosal immune system. This provides a potential mechanism for the observation of stress-induced disease recurrence in Crohn's disease.
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Catecholamines play diverse roles in host physiology, including the stress-induced fight-or-flight response, influencing gut integrity, and affecting host motivational behavior and decision-making.
“Catecholamines play diverse roles in host physiology, ranging from the stress-induced fight-or-flight response (Starkman et al., 1990) to influencing gut integrity (Meddings and Swain, 2000) and affecting host motivational behavior as well as decision-making (Terbeck et al., 2016).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Meddings and Swain, 2000
The citation is attached to the claim that catecholamines influence gut integrity. In “Pharmacologic Blockade of Glucocorticoid Effects” (page unavailable), the paper distinguishes adrenal cortical from medullary hormones and reports that blocking glucocorticoid receptors prevented stress-induced increases in gastrointestinal permeability. The Discussion likewise attributes the effect in intact rats to glucocorticoids, not catecholamines. (LLM, conf=0.86)
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References 33 · Cited by 269
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- Authors
- Meddings, J. B., & Swain, M. G.
- Affiliations
- University of Calgary (CA)
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2000-10
- Volume
- 119
- Issue
- 4
- Pages
- 1019-1028
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2030707095
- Cited by
- 269
- References
- 33
- Citations by year
- 2026: 7 · 2025: 3 · 2024: 5 · 2023: 20 · 2022: 13 · 2021: 15 · 2020: 10 · 2019: 19 · 2018: 7 · 2017: 10 · 2016: 12 · 2015: 9 · 2014: 9 · 2013: 11 · 2012: 14
- FWCI
- 3.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Calgary
- Alberta Heritage Foundation for Medical Research
- Medical Research Council Canada
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- gastrointestinal permeability, psychological stress, environmental stress, endogenous glucocorticoids, adrenal corticosteroids, intestinal epithelial barrier, Crohn's disease, recurrence, adrenalectomy, dexamethasone, mucosal immune system
- MeSH terms
- Adrenal Cortex Hormones, Adrenalectomy, Animals, Crohn Disease, Dexamethasone, Disease Models, Animal, Glucocorticoids, Intestinal Absorption, Intestines, Male, Permeability, Restraint, Physical, Stomach, Stress, Psychological, Rats, Wistar, Rats
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