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Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression
文献类型：期刊论文
| 作者 | Wang, Xinyi4; Sun, Guangqiang4; Feng, Teng4; Zhang, Jing4; Huang, Xun1 ; Wang, Tao2,3; Xie, Zuoquan1; Chu, Xingkun4; Yang, Jun4; Wang, Huan1
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| 刊名 | CELL RESEARCH
 |
| 出版日期 | 2019-10-01 |
| 卷号 | 29期号:10页码:787-803 |
| ISSN号 | 1001-0602 |
| DOI | 10.1038/s41422-019-0216-x |
| 通讯作者 | Geng, Meiyu(mygeng@simm.ac.cn) |
| 英文摘要 | Recently, increasing evidence has suggested the association between gut dysbiosis and Alzheimer's disease (AD) progression, yet the role of gut microbiota in AD pathogenesis remains obscure. Herein, we provide a potential mechanistic link between gut microbiota dysbiosis and neuroinflammation in AD progression. Using AD mouse models, we discovered that, during AD progression, the alteration of gut microbiota composition leads to the peripheral accumulation of phenylalanine and isoleucine, which stimulates the differentiation and proliferation of pro-inflammatory T helper 1 (Th1) cells. The brain-infiltrated peripheral Th1 immune cells are associated with the M1 microglia activation, contributing to AD-associated neuroinflammation. Importantly, the elevation of phenylalanine and isoleucine concentrations and the increase of Th1 cell frequency in the blood were also observed in two small independent cohorts of patients with mild cognitive impairment (MCI) due to AD. Furthermore, GV-971, a sodium oligomannate that has demonstrated solid and consistent cognition improvement in a phase 3 clinical trial in China, suppresses gut dysbiosis and the associated phenylalanine/isoleucine accumulation, harnesses neuroinflammation and reverses the cognition impairment. Together, our findings highlight the role of gut dysbiosis-promoted neuroinflammation in AD progression and suggest a novel strategy for AD therapy by remodelling the gut microbiota. |
| WOS关键词 | CENTRAL-NERVOUS-SYSTEM ; TRANSGENIC MICE ; AMYLOID-BETA ; MOUSE MODELS ; IMMUNE CELLS ; TAU ; NEURODEGENERATION ; INFLAMMATION ; MICROGLIA ; PATHOLOGY |
| 资助项目 | Personalized Medicines-Molecular Signature-based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12040101] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program of China[2015ZX09101003] |
| WOS研究方向 | Cell Biology |
| 语种 | 英语 |
| 出版者 | NATURE PUBLISHING GROUP |
| WOS记录号 | WOS:000488531600005 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/282633]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Geng, Meiyu |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Shanghai Jiao Tong Univ, Shanghai Mental Hlth Ctr, Dept Geriatr Psychiat, Sch Med, Shanghai 200025, Peoples R China 3.Shanghai Jiao Tong Univ, Alzheimers Dis & Related Disorders Ctr, Shanghai 200025, Peoples R China 4.Shanghai Green Valley Pharmaceut Co Ltd, Shanghai 201203, Peoples R China 5.Chinese Acad Sci, Inst Technol Serv Ctr, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Xinyi,Sun, Guangqiang,Feng, Teng,et al. Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression[J]. CELL RESEARCH,2019,29(10):787-803. |
| APA | Wang, Xinyi.,Sun, Guangqiang.,Feng, Teng.,Zhang, Jing.,Huang, Xun.,...&Geng, Meiyu.(2019).Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression.CELL RESEARCH,29(10),787-803. |
| MLA | Wang, Xinyi,et al."Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression".CELL RESEARCH 29.10(2019):787-803. |
入库方式： OAI收割
来源：上海药物研究所
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