Effect of Clostridium butyricum against Microglia-Mediated Neuroinflammation in Alzheimer's Disease via Regulating Gut Microbiota and Metabolites Butyrate
Sun, Xu, Yang, Chen, Kong, Fang, Gong, Wang, Ling, Liu (2020) Effect of Clostridium butyricum against Microglia-Mediated Neuroinflammation in Alzheimer's Disease via Regulating Gut Microbiota and Metabolites Butyrate Mol Nutr Food Res (IF: 5.2) 64(2) e1900636Abstract
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.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.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.© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Links
http://www.ncbi.nlm.nih.gov/pubmed/31835282http://dx.doi.org/10.1002/mnfr.201900636