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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 115; no. 13; pp. E2960 - E2969
• Main Authors: Gao, Xinghua, Cao, Qiuhua, Cheng, Yan, Zhao, Dandan, Wang, Zhuo, Yang, Hongbao, Wu, Qijin, You, Linjun, Wang, Yue, Lin, Yanting, Li, Xianjing, Wang, Yun, Bian, Jin-Song, Sun, Dongdong, Kong, Lingyi, Birnbaumer, Lutz, Yang, Yong
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 27.03.2018
• Series: PNAS Plus
• Subjects: Animals; Antibiotics; Biological Sciences; Blood circulation; Body weight; Colitis; Colitis - etiology; Colitis - pathology; Dextran; Dextran sulfate; Dextran Sulfate - toxicity; Disease Models, Animal; Gastrointestinal Microbiome - immunology; Immune system; Immunity, Innate - immunology; Infiltration; Inflammation - etiology; Inflammation - pathology; Inflammatory bowel disease; Inflammatory bowel diseases; Interleukin 6; Interleukin-6 - physiology; Intestinal microflora; Intestine; Lamina propria; Leukocytes; Leukocytes (neutrophilic); Lymph nodes; Lymphocytes B; Lysozyme; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microbiota; Mucin; Mucin-2 - metabolism; Muramidase - metabolism; PNAS Plus; Sodium; Stat3 protein; STAT3 Transcription Factor - metabolism; Stress; Stress, Physiological; Stresses; Thymus; immune reaction; DSS-induced colitis; chronic stress; gut microbiota; mucin-2
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1720696115

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 ly6Chi 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.