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

• Published in: Journal of neuroinflammation Vol. 16; no. 1; p. 201
• Main Authors: Takahashi, Kohei, Nakagawasai, Osamu, Nemoto, Wataru, Odaira, Takayo, Sakuma, Wakana, Onogi, Hiroshi, Nishijima, Hiroaki, Furihata, Ryuji, Nemoto, Yukio, Iwasa, Hiroyuki, Tan-No, Koichi, Tadano, Takeshi
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 31.10.2019; BioMed Central; BMC
• Subjects: Animals; Antidepressant; Apoptosis; Brain - immunology; Brain - metabolism; Brain - pathology; Care and treatment; Colitis - chemically induced; Colitis - microbiology; Colitis - physiopathology; Complications and side effects; Depression (Mood disorder); Depression - etiology; Depression - physiopathology; Dextran Sulfate - toxicity; EF-2001; Enterococcus; Enterococcus faecalis; Health aspects; Inflammation; Inflammatory bowel disease; Male; Mice; Microbiota (Symbiotic organisms); Neurogenesis; Neuroimmunomodulation - physiology; Neuroinflammation; Risk factors; Testing; Ulcerative colitis; Japan; Antidepressant; Inflammatory bowel disease; EF-2001; Neuroinflammation; Neurogenesis; Apoptosis
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/s12974-019-1580-7

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; 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. We 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. Treatment 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. EF-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.