Gastroenterology

Gastroenterology

Volume 119, Issue 4, October 2000, Pages 1019-1028
Gastroenterology

Alimentary Tract
Environmental stress–induced gastrointestinal permeability is mediated by endogenous glucocorticoids in the rat,☆☆,

https://doi.org/10.1053/gast.2000.18152Get rights and content

Abstract

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.

GASTROENTEROLOGY 2000;119:1019-1028

Section snippets

Animals

Male Wistar rats were purchased (Charles River, St. Constant, Quebec, Canada) and housed in the University of Calgary Animal Care Center. Animals were allowed to acclimatize to the facility for 2 weeks unless otherwise noted and were handled daily by the same individuals who performed the experiments. On most days the animals were housed in gang cages, but during permeability testing they were placed in individual metabolic cages for urine collection. To acclimatize them to this, the daily

Animal acclimatization

Transport of animals is a stressful situation, and we took advantage of this to sequentially follow gastrointestinal permeability after arrival at the Animal Care Center. These data are presented in a standard format illustrating the fractional excretion of sucrose (gastric permeability; Figure 1A), lactulose-mannitol ratio (small intestinal permeability; Figure 1B), and fractional excretion of sucralose (small intestinal and colonic permeability; Figure 1C).

. Gastrointestinal permeability after

Discussion

These data provide convincing support for the hypothesis that environmental stress can increase gastrointestinal permeability. Swimming stress constitutes a more profound form of stress than does restraint,24 and as illustrated in Figure 3, there was a significantly increased adrenal glucocorticoid response to this degree of stress. Not only was there a dose-response relationship between the degree of stress and plasma corticosterone concentration, but also with the elicited permeability

Acknowledgements

The authors thank Kim Tran, Tai Le, and Ian Gibbons for their technical expertise in the performance of these studies.

References (33)

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Supported by generous grants from the Medical Research Council of Canada and Searle Canada Inc.

☆☆

Address requests for reprints to: Jon Meddings, M.D., 1705 Health Sciences Center, 3330 Hospital Drive N.W., Calgary, Alberta, Canada T2N 4N1. e-mail: [email protected]; fax: (403) 220-8747.

Dr. Meddings is an Alberta Heritage Foundation Medical Senior Scholar, and Dr. Swain is a Medical Research Council Medical Scholar and an AHFMR Clinical Investigator.

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