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

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 (Rib^high-L.m.) particularly enriched in 5XFAD transgenic mice. Mechanistically, Rib^high-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 activ

SUBMITTER: Wang X 

PROVIDER: S-EPMC11573985 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature