Akkermansia muciniphila Protects Against Psychological Disorder-Induced Gut Microbiota-Mediated Colonic Mucosal Barrier Damage and Aggravation of Colitis.

Tuo Chen,Zhenglan Duan,Guoping Shi,Lei Zhu,Jinyong Zhou,Zeyu Feng,Yugen Chen,Fan Bu,Rong Wang,Li Liu,Qing Ni,Qiong Wang,Yang Ding,Xiaomin Yuan

doi:10.3389/fcimb.2021.723856

Abstract

Psychological disorders are associated with increased risk of severe inflammatory bowel disease (IBD) by causing gut microbiota dysbiosis and colonic mucosal barrier damage. However, the interaction between chronic restraint stress (CRS), gut microbiota composition, and colonic mucus remains unclear. We demonstrated that mice under CRS conditions exhibited alterations in microbiota composition, disruption of colonic mucus, and aggravation of colitis. In addition, the abundance of Akkermansia muciniphila was significantly decreased in mice under CRS and UC patients with depression, and positively associated with the expression of MUC2. After antibiotic treatment, the recipient mice colonized with CRS microbiota showed barrier defects and severe colitis. Administration of Akkermansia muciniphila was found to restore colonic mucus and modify the gut microbiota. We confirm that CRS-mediated gut microbiota dysbiosis results in colonic mucosal barrier damage and aggravation of colitis. Our results suggest that A. muciniphila is expected to be a potential probiotic to protect and treat colonic mucus that is involved in IBD with psychological disorders.

Highlights

Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn’s disease (CD), has become a global burden with rapidly increasing morbidity in the past 20 years
Our results reveal that chronic restraint stress (CRS), a credible procedure for establishing a model of depression in mice, induced alterations in gut microbiota and dysfunction in the colonic mucosal barrier and prompted the development of experimental colitis
We demonstrated that CRS aggravates dextran sodium sulfate (DSS)-induced colitis with shorter colon length, higher histopathological scores, colonic mucus damage, and gut microbiota dysbiosis

Summary

Introduction

Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn’s disease (CD), has become a global burden with rapidly increasing morbidity in the past 20 years. Epidemiological surveys indicate that established prevalence populations of IBD occur in 1.5 million people in American and 2.2 million in Europe, and affected populations are gradually growing worldwide Numerous studies have demonstrated that a high frequency of psychological disorder, such as depression or anxiety, is observed in IBD patients. Depression affects an estimated over 25% persons with IBD, and two to three times higher than healthy individuals (Walker et al, 2008). Mechanisms behind the role of psychological disorders or depression in the aggravation of IBD are underexplored

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