Jing Sun1, Jingxuan Xu2, Bo Yang3, Keyang Chen1, Yu Kong3, Na Fang3, Tianyu Gong3, Fangyan Wang4, Zongxin Ling5, Jiaming Liu3,1. 1. Department of Neurology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China. 2. Department of Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China. 3. Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, Wenzhou, 325035, China. 4. Departments of Pathophysiology, School of Basic Medicine Science, Wenzhou Medical University, Wenzhou, 325035, China. 5. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.
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.
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.
Authors: Henry Yue Hong Meng; Christopher Chi Hang Mak; Wing Yan Mak; Tao Zuo; Ho Ko; Francis Ka Leung Chan Journal: Eur J Nutr Date: 2022-01-10 Impact factor: 5.614
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Authors: Claire E Sexton; Kaarin J Anstey; Filippo Baldacci; C J Barnum; Anna M Barron; Kaj Blennow; Henry Brodaty; Samantha Burnham; Fanny M Elahi; Jürgen Götz; Yun-Hee Jeon; Maya Koronyo-Hamaoui; Susan M Landau; Nicola T Lautenschlager; Simon M Laws; Darren M Lipnicki; Hanzhang Lu; Colin L Masters; Wendy Moyle; Akinori Nakamura; Giulio Maria Pasinetti; Naren Rao; Christopher Rowe; Perminder S Sachdev; Peter R Schofield; Einar M Sigurdsson; Kate Smith; Velandai Srikanth; Cassandra Szoeke; Malú G Tansey; Rachel Whitmer; Donna Wilcock; Tien Y Wong; Lisa J Bain; Maria C Carrillo Journal: Alzheimers Dement Date: 2021-05-31 Impact factor: 16.655