Kai-Xin-San polysaccharides exert therapeutic effects on D-gal and Aβ25-35-induced AD rats by regulating gut microbiota and metabolic profile

Metabolic abnormalities and gut microbiota imbalance are intricately linked to the onset and progression of Alzheimer's disease (AD). Kai-Xin-San (KXS) is a traditional herbal formula known for its therapeutic effects on AD. Our previous research indicated that Kai-Xin-San polysaccharide (KXS-P) exhibits a significant therapeutic impact on AD, but the precise mechanisms remain incompletely understood. In this study, untargeted fecal metabolomics and 16S rRNA gene sequencing were used to investigate the potential mechanisms by which KXS-P acts against AD. Key metabolites and gut microbial species were identified using multivariate analysis and a comprehensive examination of intestinal microecology. Our findings revealed that KXS-P improves lipid metabolism in AD rats by modulating a series of lipid molecules and bile acid levels. Additionally, KXS-P regulated gut microbiota composition and restored the symbiotic relationships within the gut microbiome. Notably, the antiinflammatory effect of KXS-P may be related to its regulation of specific lipotypes levels and the abundance of Romboutsia, Bifidobacterium and Alloprevotella. KXS-P demonstrates the ability to alleviate symptoms of AD rats through multiple mechanisms: (1) Improving lipid metabolism and maintaining lipid homeostasis; (2) Reducing neuronal and inflammatory damage; (3) Regulating the composition and symbiotic relationships of gut microbiota to preserve intestinal microecological balance.