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Effect of Clostridium butyricum against Microglia‐Mediated Neuroinflammation in Alzheimer's Disease via Regulating Gut Microbiota and Metabolites Butyrate
Author(s) -
Sun Jing,
Xu Jingxuan,
Yang Bo,
Chen Keyang,
Kong Yu,
Fang Na,
Gong Tianyu,
Wang Fangyan,
Ling Zongxin,
Liu Jiaming
Publication year - 2020
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201900636
Subject(s) - neuroinflammation , butyrate , microglia , proinflammatory cytokine , gut–brain axis , gut flora , clostridium butyricum , tumor necrosis factor alpha , immunology , chemistry , biology , inflammation , biochemistry , fermentation
Scope Recent evidences demonstrate that abnormal gut microbiota (GM) might be involved in the pathogenesis of Alzheimer's disease (AD). However, the role of probiotics in preventing AD by regulating GM–gut–brain axis remains unclear. Here, the anti‐neuroinflammatory effect and its mechanism of probiotic Clostridium butyricum (CB) against AD is investigated by regulating GM–gut–brain axis. Methods and results APPswe/PS1dE9 (APP/PS1) transgenic are treated intragastrically with CB for 4 weeks then cognitively tested. Amyloid‐β (Aβ) burden, microglial activation, proinflammatory cytokines production, GM, and metabolites butyrate are analyzed. Moreover, Aβ‐induced BV2 microglia are pretreated with butyrate, and the levels of cluster of differentiation 11b (CD11b), cyclooxygenase‐2 (COX‐2), and NF‐κB p65 phosphorylation are determined. The results show that CB treatment prevents cognitive impairment, Aβ deposits, microglia activation, and production of tumor necrosis factor (TNF)‐α and interleukin (IL)‐1β in the brain of APP/PS1 mice. Meanwhile, abnormal GM and butyrate are reversed after CB treatment. Notably, butyrate treatment reduces the levels of CD11b and COX‐2, and suppresses phosphorylation of NF‐κB p65 in the Aβ‐induced BV2 microglia. Conclusions These findings indicate that CB treatment could attenuate microglia‐mediated neuroinflammation via regulating the GM–gut–brain axis, which is mediated by the metabolite butyrate.