Disturbance in the Mucosa-Associated Commensal Bacteria Is Associated with the Exacerbation of Chronic Colitis by Repeated Psychological Stress; Is That the New Target of Probiotics?

Sohei Arase,Mitsuhisa Kawai,Yohei Watanabe,Hiromi Setoyama,Noriko Nagaoka,Satoshi Matsumoto,Fabio Cominelli

doi:10.1371/journal.pone.0160736

Abstract

Psychological stress can exacerbate inflammatory bowel disease. However, the mechanisms underlying how psychological stress affects gut inflammation remain unclear. Here, we focused on the relationship between changes in the microbial community of mucosa-associated commensal bacteria (MACB) and mucosal immune responses induced by chronic psychological stress in a murine model of ulcerative colitis. Furthermore, we examined the effect of probiotic treatment on exacerbated colitis and MACB composition changes induced by chronic psychological stress. Repeated water avoidance stress (rWAS) in B6-Tcra-/- mice severely exacerbated colitis, which was evaluated by both colorectal tissue weight and histological score of colitis. rWAS treatment increased mRNA expression of UCN2 and IFN-γ in large intestinal lamina propria mononuclear cells (LI-LPMC). Interestingly, exacerbated colitis was associated with changes in the microbial community of MACB, specifically loss of bacterial species diversity and an increase in the component ratio of Clostridium, revealed by 16S rRNA gene amplicon analysis. Finally, the oral administration of a probiotic Lactobacillus strain was protective against the exacerbation of colitis and was associated with a change in the bacterial community of MACB in rWAS-exposed Tcra-/- mice. Taken together, these results suggested that loss of species diversity in MACB might play a key role in exacerbated colitis induced by chronic psychological stress. In addition, probiotic treatment may be used as a tool to preserve the diversity of bacterial species in MACB and alleviate gut inflammation induced by psychological stress.

Highlights

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), is an intractable disease in the modern society [1]
We found that gene expression of UCN2 and CRHR2, were significantly increased in LI-LPMCs of mice subjected to repeated water avoidance stress (rWAS) (Table 2)
We examined the effects of rWAS on physiological conditions in C57BL/6 mice. rWAS exposure increased the gene expression levels of IFN-γ, UCN2 and CRHR2 in LI-LPMCs (S2 Table); there was no sign of colitis in C57BL/6 mice (S2A Fig)

Summary

Introduction

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), is an intractable disease in the modern society [1]. Chronic inflammation associated with IBD follows a course of relapse and remission, and longstanding IBD has been shown to increase the risk of colorectal cancer [2]. Exposure to psychological stress has been shown to exacerbate dextran sulfate sodium (DSS)–induced colitis in the murine model [4]. It remains unclear how psychological stress affects gut inflammation. There are many studies suggesting that gastrointestinal (GI) microbiota is involved in the development and exacerbation of chronic colitis [5]. Involvement of GI microbiota has been implicated in gut inflammation, and in colorectal cancer, type 1 diabetes, and obesity [7]. It has been speculated that changes in the gut microbiota alters mucosal permeability, which results in dysfunction of immune responses in the colonic mucosa [8]

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Conclusion