Chronic stress promotes colitis by disturbing the gut microbiota and triggering immune system response

Abstract

<p id="d7622854e561">Stress cannot be avoided in the present competitive world, and chronic stress is associated with detrimental effects on physical health, including the progression of inflammatory bowel disease (IBD). However, the mechanisms behind it are less clearly understood. This study showed that chronic stress disturbed gut microbiota, thereby triggering immune system response and facilitating dextran sulfate sodium-induced colitis. Results also showed stress-deficient expression of mucin-2 and lysozyme, which may contribute to the disorder of gut microbiota. This study adds to our understanding of interactions between microbiota and host and provides the basis for future clinical studies of microbiota manipulation and transplantation and the development of new therapeutic strategies for depression or IBD. </p><p class="first" id="d7622854e564">Chronic stress is known to promote inflammatory bowel disease (IBD), but the underlying mechanism remains largely unresolved. Here, we found chronic stress to sensitize mice to dextran sulfate sodium (DSS)-induced colitis; to increase the infiltration of B cells, neutrophils, and proinflammatory ly6C ^hi macrophages in colonic lamina propria; and to present with decreased thymus and mesenteric lymph node (MLN) coefficients. Circulating total white blood cells were significantly increased after stress, and the proportion of MLN-associated immune cells were largely changed. Results showed a marked activation of IL-6/STAT3 signaling by stress. The detrimental action of stress was not terminated in IL-6 ^−/− mice. Interestingly, the composition of gut microbiota was dramatically changed after stress, with expansion of inflammation-promoting bacteria. Furthermore, results showed stress-induced deficient expression of mucin-2 and lysozyme, which may contribute to the disorder of gut microbiota. Of note is that, in the case of cohousing, the stress-induced immune reaction and decreased body weight were abrogated, and transferred gut microbiota from stressed mice to control mice was sufficient to facilitate DSS-induced colitis. The important role of gut microbiota was further reinforced by broad-spectrum antibiotic treatment. Taken together, our results reveal that chronic stress disturbs gut microbiota, triggering immune system response and facilitating DSS-induced colitis. </p>