Chronic stress induces mast cell-dependent bacterial adherence and initiates mucosal inflammation in rat intestine

Background & Aims: Chronic psychological stress is an important factor in relapses of intestinal disorders, but it remains unclear if stress can induce primary gut inflammation in a previously healthy host. Methods: Mast cell-deficient (Ws/Ws) rats and wild-type control (+/+) rats were submitted to water avoidance stress or sham stress (1 h/day) for 10 consecutive days, as a model of ongoing life stress. Results: Both rat groups had similar systemic responses to stress, as assessed by changes in weight, corticosterone levels, and defecation. In +/+ rats, chronic stress induced barrier dysfunction in the ileum and colon (increased macromolecular permeability and depletion of mucus) and ultrastructural changes in epithelial cells (enlarged mitochondria and presence of autophagosomes) associated with bacterial adhesion and penetration into enterocytes. Moreover, hyperplasia and activation of mast cells, infiltration of neutrophils and mononuclear cells, and increased myeloperoxidase (MPO) activity were documented in the mucosa. In intestine of Ws/Ws rats, epithelial function and morphology were unchanged by chronic stress, bacteria I-epithelial cell interaction was not demonstrated, and there was no evidence of inflammatory cell infiltration. Conclusions: These findings suggest that chronic psychological stress can be an initiating factor in intestinal inflammation by impairing mucosal defenses against luminal bacteria and highlight the importance of mast cells in this process.