Effect of <i>Clostridium butyricum</i> against Microglia‐Mediated Neuroinflammation in Alzheimer's Disease via Regulating Gut Microbiota and Metabolites Butyrate

Abstract

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.