Environmental stress-induced gastrointestinal permeability is mediated by endogenous glucocorticoids in the rat

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.