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Sodium oligomannate disrupts the adherence of Ribhigh bacteria to gut epithelia to block SAA-triggered Th1 inflammation in 5XFAD transgenic mice

文献类型：期刊论文

作者Wang, Xinyi1,10; Xie, Zuoquan1; Yuan, Jie10; Jin, Enjing10; Lian, Wen10; Chang, Shuaishuai10; Sun, Guangqiang10; Feng, Zhengnan10; Xu, Hui1; Du, Chen10
刊名CELL DISCOVERY
出版日期2024-11-19
卷号10期号:1页码:19
DOI10.1038/s41421-024-00725-5
英文摘要Sodium oligomannate (GV-971), an oligosaccharide drug approved in China for treating mild-to-moderate Alzheimer's disease (AD), was previously found to recondition the gut microbiota and limit altered peripheral Th1 immunity in AD transgenic mice. As a follow-up study, we here made advances by pinpointing a Lactobacillus murinus (L.m.) strain that highly expressed a gene encoding a putative adhesin containing Rib repeats (Ribhigh-L.m.) particularly enriched in 5XFAD transgenic mice. Mechanistically, Ribhigh-L.m. adherence to the gut epithelia upregulated fecal metabolites, among which lactate ranked as the top candidate. Excess lactate stimulated the epithelial production of serum amyloid A (SAA) in the gut via the GPR81-NF kappa B axis, contributing to peripheral Th1 activation. Moreover, GV-971 disrupted the adherence of Ribhigh-L.m. to gut epithelia via direct binding to Rib, which corrected the excess lactate, reduced SAA, and alleviated Th1-skewed inflammation. Together, we gained further insights into the molecular link between gut bacteria and AD progression and the mechanism of GV-971 in treating AD.
WOS关键词MICROBIOTA ; HEALTH ; IDENTIFICATION ; EXPRESSION ; DEMENTIA ; ADHESION ; RECEPTOR ; DISEASE ; PROTEIN ; SYSTEM
资助项目National Natural Science Foundation of China (National Science Foundation of China)[81821005] ; Natural Science Foundation of China for Innovation Research Group[LG202101-01-01] ; Natural Science Foundation of China for Innovation Research Group[LG-GG-202204-01] ; Shanghai Municipal Science and Technology Major Project, Lingang Laboratory ; Haibo Plan Postdoctoral Science and Research Innovation Project ; Shanghai Pudong New District Science and Technology Development Fund
WOS研究方向Cell Biology
WOS记录号WOS:001357786800001
出版者SPRINGERNATURE
源URL[http://119.78.100.183/handle/2S10ELR8/314509]  
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, Peoples R China
2.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai, Shandong, Peoples R China
3.Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Gerontol, Shanghai, Peoples R China
4.Shanghai Jiao Tong Univ, Affect Disorder Ctr, Sch Med, Dept Psychiat,Ruijin Hosp, Shanghai, Peoples R China
5.Lingang Lab, Shanghai, Peoples R China
6.Univ Chinese Acad Sci, Beijing, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai, Peoples R China
8.China Pharmaceut Univ, Sch Pharm, Nanjing, Jiangsu, Peoples R China
9.Chinese Acad Sci, Shanghai Inst Mat Med, Inst Technol Serv Ctr, Shanghai, Peoples R China
10.Shanghai Green Valley Pharmaceut Co Ltd, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Xinyi,Xie, Zuoquan,Yuan, Jie,et al. Sodium oligomannate disrupts the adherence of Ribhigh bacteria to gut epithelia to block SAA-triggered Th1 inflammation in 5XFAD transgenic mice[J]. CELL DISCOVERY,2024,10(1):19.
APA Wang, Xinyi.,Xie, Zuoquan.,Yuan, Jie.,Jin, Enjing.,Lian, Wen.,...&Geng, Meiyu.(2024).Sodium oligomannate disrupts the adherence of Ribhigh bacteria to gut epithelia to block SAA-triggered Th1 inflammation in 5XFAD transgenic mice.CELL DISCOVERY,10(1),19.
MLA Wang, Xinyi,et al."Sodium oligomannate disrupts the adherence of Ribhigh bacteria to gut epithelia to block SAA-triggered Th1 inflammation in 5XFAD transgenic mice".CELL DISCOVERY 10.1(2024):19.

入库方式： OAI收割

来源：上海药物研究所

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