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

Abstract

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 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.

Unique maternal immune and functional microbial profiles during prenatal stress

“…While our group 25 and others 26 have shown that prenatal stress can alter maternal fecal microbial populations, the intestinal microbial community has not yet been fully explored in the context of prenatal stress. Largely, our data stand in contrast to recent studies that have highlighted stark decreases in immune-modulatory bacterial groups such as Lactobacillus 73,74 , as well as exacerbations in inflammatory severity upon exposure to stress 75,76 . The previously accepted belief was that psychological stress exacerbated GI inflammation, an outcome that can also be observed clinically given the propensity for stressful life events to be associated with relapse in inflammatory bowel disease 77 .…”

Gut microbiota requires vagus nerve integrity to promote depression

“…While the exact underlying cascades of events are not elucidated, we found that the transmitted dysbiosis requires an intact vagus nerve to be effective. Our results are in line with recent studies showing altered cecal and fecal microbiota composition in experimental models of stress (16,17) and in depressed patients (18). These alterations may contribute to the neuroprogression of stress-related depression by altering physiological and/or metabolism processes that activate vagal afferents, such as microbial peptides, neurotransmitter release and immunity/inflammation (19,20).…”

Short‐chain fatty acids: microbial metabolites that alleviate stress‐induced brain–gut axis alterations

“…These findings have particular relevance for chronic stress‐induced gastrointestinal dysfunction, as chronic stress has previously been shown to promote colitis in mice (Gao et al . ), and chronic stress is associated with an increased risk of functional gastrointestinal disorders in humans, as well as increased rates of relapse and surgery for inflammatory bowel diseases (Stam et al . ; Klooker et al .…”

“…Another explanation for the discrepancy between in vivo intestinal permeability and LBP levels could be handling stress induced by the administration of FITC-Dextran in the in vivo intestinal permeability test, as stress-responsiveness was increased in the stress group, and as stress signalling has been shown to induce intestinal permeability (Rodino-Janeiro et al 2015). These findings J Physiol 596.20 have particular relevance for chronic stress-induced gastrointestinal dysfunction, as chronic stress has previously been shown to promote colitis in mice (Gao et al 2018), and chronic stress is associated with an increased risk of functional gastrointestinal disorders in humans, as well as increased rates of relapse and surgery for inflammatory bowel diseases (Stam et al 1997;Klooker et al 2009;Bernstein, 2017). It must be noted though that heightened right colonic fermentation has been shown to be a potential pathophysiological factor in irritable bowel syndrome (Farmer et al 2014;Ringel-Kulka et al 2015).…”