| First Author | Wang X | Year | 2024 |
| Journal | Cell Discov | Volume | 10 |
| Issue | 1 | Pages | 115 |
| PubMed ID | 39557828 | Mgi Jnum | J:360720 |
| Mgi Id | MGI:7787215 | Doi | 10.1038/s41421-024-00725-5 |
| Citation | Wang X, et al. (2024) Sodium oligomannate disrupts the adherence of Rib(high) bacteria to gut epithelia to block SAA-triggered Th1 inflammation in 5XFAD transgenic mice. Cell Discov 10(1):115 |
| abstractText | 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-NFkappaB axis, contributing to peripheral Th1 activation. Moreover, GV-971 disrupted the adherence of Rib(high)-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. |
