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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

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

Authors :
Xinyi Wang
Zuoquan Xie
Jie Yuan
Enjing Jin
Wen Lian
Shuaishuai Chang
Guangqiang Sun
Zhengnan Feng
Hui Xu
Chen Du
Xinying Yang
Aihua Xia
Ji Qiu
Qingli Zhang
Feifei Lin
Jia Liu
Liang Li
Xiaoguang Du
Zhongping Xiao
Zhou Yi
Zhiyu Luo
Changrong Ge
Rui Li
Mingyue Zheng
Yi Jiang
Tao Wang
Jing Zhang
Qihao Guo
Meiyu Geng
Source :
Cell Discovery, Vol 10, Iss 1, Pp 1-19 (2024)
Publication Year :
2024
Publisher :
Nature Publishing Group, 2024.

Abstract

Abstract 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-NFκB 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.

Subjects

Subjects :
Cytology
QH573-671

Details

Language :
English
ISSN :
20565968
Volume :
10
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Cell Discovery
Publication Type :
Academic Journal
Accession number :
edsdoj.6249bc9a6787423f8652523de23baadc
Document Type :
article
Full Text :
https://doi.org/10.1038/s41421-024-00725-5