Effect of Enterococcus faecalis 2001 on colitis and depressive-like behavior in dextran sulfate sodium-treated mice: involvement of the brain\u2013gut axis

Kohei Takahashi,Takeshi Tadano,Hiroyuki Iwasa,Yukio Nemoto,Wataru Nemoto,Hiroaki Nishijima,Osamu Nakagawasai,Wakana Sakuma,Hiroshi Onogi,Ryuji Furihata,Koichi Tan-No,Takayo Odaira

doi:10.1186/s12974-019-1580-7

Abstract

BackgroundPatients with inflammatory bowel disease (IBD), including those with ulcerative colitis and Crohn’s disease, have higher rates of psychiatric disorders, such as depression and anxiety; however, the mechanism of psychiatric disorder development remains unclear. Mice with IBD induced by dextran sulfate sodium (DSS) in drinking water exhibit depressive-like behavior. The presence of Lactobacillus in the gut microbiota is associated with major depressive disorder. Therefore, we examined whether Enterococcus faecalis 2001 (EF-2001), a biogenic lactic acid bacterium, prevents DSS-induced depressive-like behavior and changes in peripheral symptoms.MethodsWe evaluated colon inflammation and used the tail suspension test to examine whether EF-2001 prevents IBD-like symptoms and depressive-like behavior in DSS-treated mice. The protein expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), X-linked inhibitor of apoptosis protein (XIAP), and cleaved caspase-3 in the rectum and hippocampus was assessed by western blotting. Hippocampal neurogenesis, altered nuclear factor-kappa B (NFκB) p65 morphometry, and the localization of activated NFκB p65 and XIAP were examined by immunohistochemistry.ResultsTreatment with 1.5% DSS for 7 days induced IBD-like pathology and depressive-like behavior, increased TNF-α and IL-6 expression in the rectum and hippocampus, activated caspase-3 in the hippocampus, and decreased hippocampal neurogenesis. Interestingly, these changes were reversed by 20-day administration of EF-2001. Further, EF-2001 administration enhanced NFκB p65 expression in the microglial cells and XIAP expression in the hippocampus of DSS-treated mice.ConclusionEF-2001 prevented IBD-like pathology and depressive-like behavior via decreased rectal and hippocampal inflammatory cytokines and facilitated the NFκB p65/XIAP pathway in the hippocampus. Our findings suggest a close relationship between IBD and depression.

Highlights

Patients with inflammatory bowel disease (IBD), including those with ulcerative colitis and Crohn’s disease, have higher rates of psychiatric disorders, such as depression and anxiety; the mechanism of psychiatric disorder development remains unclear
We evaluated the predictive validity of the IBD animal model by using a classic antidepressant drug, Imi, or a steroid, Dex
These results demonstrated that dextran sulfate sodium (DSS)-treated mice provided a model of IBD with depression

Summary

Introduction

Patients with inflammatory bowel disease (IBD), including those with ulcerative colitis and Crohn’s disease, have higher rates of psychiatric disorders, such as depression and anxiety; the mechanism of psychiatric disorder development remains unclear. Mice with IBD induced by dextran sulfate sodium (DSS) in drinking water exhibit depressive-like behavior. We examined whether Enterococcus faecalis 2001 (EF-2001), a biogenic lactic acid bacterium, prevents DSS-induced depressive-like behavior and changes in peripheral symptoms. Inflammatory bowel disease (IBD), which comprises ulcerative colitis and Crohn’s disease, affects approximately 2.2 million people in Europe and 1.4 million people in the USA. Other researchers have demonstrated that chronic experimental colitis increases anxiety behavior in mice [3]. Peripheral inflammation may account for at least some of the neurological and behavioral changes associated with chronic inflammatory diseases. Patients with IBD have higher rates of obsessive–compulsive disorder, panic disorder, depression, and anxiety [4,5,6,7]

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