Mucosal immunosuppression and epithelial barrier defects are key events in murine psychosocial stress-induced colitis

Chronic psychosocial stress is a risk factor for many affective and somatic disorders, including inflammatory bowel diseases. In support chronic subordinate colony housing (CSC, 19 days), an established mouse model of chronic psychosocial stress, causes the development of spontaneous colitis. However, the mechanisms underlying the development of such stress-induced colitis are poorly understood. Assessing several functional levels of the colon during the initial stress phase, we show a pronounced adrenal hormone-mediated local immune suppression, paralleled by impaired intestinal barrier functions, resulting in enhanced bacterial load in stool and colonic tissue. Moreover, prolonged treatment with broad-spectrum antibiotics revealed the causal role of these early maladaptations in the development of stress-induced colitis. Together, we demonstrate that translocation of commensal bacteria is crucial in the initiation of stress-induced colonic inflammation. However, aggravation by the immune-modulatory effects of fluctuating levels of adrenal hormones is required to develop this into a full-blown colitis.