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

被引：77

作者：

Takahashi, Kohei ^{[1
,2
]}

Nakagawasai, Osamu ^{[1
]}

Nemoto, Wataru ^{[1
]}

Odaira, Takayo ^{[1
]}

Sakuma, Wakana ^{[1
]}

Onogi, Hiroshi ^{[3
]}

Nishijima, Hiroaki ^{[4
]}

Furihata, Ryuji ^{[5
]}

Nemoto, Yukio ^{[6
]}

Iwasa, Hiroyuki ^{[7
]}

Tan-No, Koichi ^{[1
]}

Tadano, Takeshi ^{[1
,8
]}

机构：

[1] Tohoku Med & Pharmaceut Univ, Fac Pharmaceut Sci, Dept Pharmacol, Aoba Ku, 4-4-1 Komatsushima, Sendai, Miyagi 9818558, Japan

[2] Int Univ Hlth & Welf, Sch Pharm, Dept Pharmacol, Ohtawara, 2600-1 Kitakanemaru, Ohtawara, Tochigi 3248501, Japan

[3] Tohoku Fukushi Univ, Fac Hlth Sci, Aoba Ku, 1-8-1 Kunimi, Sendai, Miyagi 9818522, Japan

[4] Showa Univ, Sch Pharm, Dept Healthcare & Regulatory Sci, Shinagawa Ku, 1-5-8 Hatanodai, Tokyo 1428555, Japan

[5] Nihon Univ, Dept Psychiat, Sch Med, Itabashi Ku, 30-1 Oyaguchi Kamicho, Tokyo 1738610, Japan

[6] Yokohama Univ Pharm, Kampo & Herbal Med Res Ctr, Totsuka Ku, 601 Matanocho, Yokohama, Kanagawa 2450066, Japan

[7] Nihon Berm Co Ltd, Chiyoda Ku, 2-14-3 Nagatachou, Tokyo 1000014, Japan

[8] Kanazawa Univ, Grad Sch Med Sci, Complementary & Alternat Med Clin Res & Dev, Kanazawa, Ishikawa 9208640, Japan

来源：

JOURNAL OF NEUROINFLAMMATION | 2019年 / 16卷 / 01期

关键词：

Antidepressant; Apoptosis; EF-2001; Inflammatory bowel disease; Neurogenesis; Neuroinflammation; LONG-TERM DEPRESSION; HIPPOCAMPAL NEUROGENESIS; GENE-EXPRESSION; KAPPA-B; CYTOKINES; ANXIETY; PROLIFERATION; INFLAMMATION; APOPTOSIS; PATHWAYS;

D O I：

10.1186/s12974-019-1580-7

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background 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. Methods 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-alpha (TNF-alpha), 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 (NF kappa B) p65 morphometry, and the localization of activated NF kappa B p65 and XIAP were examined by immunohistochemistry. Results Treatment with 1.5% DSS for 7 days induced IBD-like pathology and depressive-like behavior, increased TNF-alpha 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 NF kappa B p65 expression in the microglial cells and XIAP expression in the hippocampus of DSS-treated mice. Conclusion EF-2001 prevented IBD-like pathology and depressive-like behavior via decreased rectal and hippocampal inflammatory cytokines and facilitated the NF kappa B p65/XIAP pathway in the hippocampus. Our findings suggest a close relationship between IBD and depression.

引用

页数：16

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[1] Low Molecular-Weight Curdlan, (1→3)-β-Glucan Suppresses TLR2-Induced RANKL-Dependent Bone Resorption [J].