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

Abstract 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 induc...

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Main Authors: Kohei Takahashi, Osamu Nakagawasai, Wataru Nemoto, Takayo Odaira, Wakana Sakuma, Hiroshi Onogi, Hiroaki Nishijima, Ryuji Furihata, Yukio Nemoto, Hiroyuki Iwasa, Koichi Tan-No, Takeshi Tadano
Format: Article
Language:English
Published: BMC 2019-10-01
Series:Journal of Neuroinflammation
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12974-019-1580-7
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author Kohei Takahashi
Osamu Nakagawasai
Wataru Nemoto
Takayo Odaira
Wakana Sakuma
Hiroshi Onogi
Hiroaki Nishijima
Ryuji Furihata
Yukio Nemoto
Hiroyuki Iwasa
Koichi Tan-No
Takeshi Tadano
author_facet Kohei Takahashi
Osamu Nakagawasai
Wataru Nemoto
Takayo Odaira
Wakana Sakuma
Hiroshi Onogi
Hiroaki Nishijima
Ryuji Furihata
Yukio Nemoto
Hiroyuki Iwasa
Koichi Tan-No
Takeshi Tadano
author_sort Kohei Takahashi
collection DOAJ
description Abstract 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-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. Results 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. Conclusion 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.
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spelling doaj.art-fcc176da7b434786ac4fb7c6a883f7152022-12-22T00:33:29ZengBMCJournal of Neuroinflammation1742-20942019-10-0116111610.1186/s12974-019-1580-7Effect of Enterococcus faecalis 2001 on colitis and depressive-like behavior in dextran sulfate sodium-treated mice: involvement of the brain–gut axisKohei Takahashi0Osamu Nakagawasai1Wataru Nemoto2Takayo Odaira3Wakana Sakuma4Hiroshi Onogi5Hiroaki Nishijima6Ryuji Furihata7Yukio Nemoto8Hiroyuki Iwasa9Koichi Tan-No10Takeshi Tadano11Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical UniversityDepartment of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical UniversityDepartment of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical UniversityDepartment of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical UniversityDepartment of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical UniversityFaculty of Health Science, Tohoku Fukushi UniversityDepartment of Healthcare and Regulatory Sciences, School of Pharmacy, Showa UniversityDepartment of Psychiatry, Nihon University School of MedicineKampo and Herbal Medicine Research Center, Yokohama University of PharmacyNihon Berm Co, Ltd, 2-14-3 NagatachouDepartment of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical UniversityDepartment of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical UniversityAbstract 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-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. Results 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. Conclusion 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.http://link.springer.com/article/10.1186/s12974-019-1580-7AntidepressantApoptosisEF-2001Inflammatory bowel diseaseNeurogenesisNeuroinflammation
spellingShingle Kohei Takahashi
Osamu Nakagawasai
Wataru Nemoto
Takayo Odaira
Wakana Sakuma
Hiroshi Onogi
Hiroaki Nishijima
Ryuji Furihata
Yukio Nemoto
Hiroyuki Iwasa
Koichi Tan-No
Takeshi Tadano
Effect of Enterococcus faecalis 2001 on colitis and depressive-like behavior in dextran sulfate sodium-treated mice: involvement of the brain–gut axis
Journal of Neuroinflammation
Antidepressant
Apoptosis
EF-2001
Inflammatory bowel disease
Neurogenesis
Neuroinflammation
title Effect of Enterococcus faecalis 2001 on colitis and depressive-like behavior in dextran sulfate sodium-treated mice: involvement of the brain–gut axis
title_full Effect of Enterococcus faecalis 2001 on colitis and depressive-like behavior in dextran sulfate sodium-treated mice: involvement of the brain–gut axis
title_fullStr Effect of Enterococcus faecalis 2001 on colitis and depressive-like behavior in dextran sulfate sodium-treated mice: involvement of the brain–gut axis
title_full_unstemmed Effect of Enterococcus faecalis 2001 on colitis and depressive-like behavior in dextran sulfate sodium-treated mice: involvement of the brain–gut axis
title_short Effect of Enterococcus faecalis 2001 on colitis and depressive-like behavior in dextran sulfate sodium-treated mice: involvement of the brain–gut axis
title_sort effect of enterococcus faecalis 2001 on colitis and depressive like behavior in dextran sulfate sodium treated mice involvement of the brain gut axis
topic Antidepressant
Apoptosis
EF-2001
Inflammatory bowel disease
Neurogenesis
Neuroinflammation
url http://link.springer.com/article/10.1186/s12974-019-1580-7
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