Gut microbiota and serum metabolomics unveil the role of Phellinus ribis polysaccharides in improving Alzheimer's disease symptoms in senescence-accelerated mice.

Alzheimer's disease (AD), a complex neurodegenerative disorder with limited therapeutic options, urgently requires innovative strategies targeting its underlying mechanisms. Phellinus ribis polysaccharides (PRG), a bioactive compound with proven neuroprotective and microbiota-modulating effects, hold promise for addressing AD pathology through gut-brain axis regulation. This study aims to investigate the effects of PRG on the gut microbiota composition and serum metabolomic profile of a senescence-accelerated mouse model (SAMP8) and to reveal its potential mechanisms in alleviating symptoms of AD. The gut microbiota composition of SAMP8 mice treated with PRG was analyzed using 16S rRNA gene sequencing. Non-targeted metabolomics, based on ultra-performance liquid chromatography quadrupole/electrostatic field orbitrap high-resolution mass spectrometry, was employed to analyze changes in metabolites in the serum samples. Spearman correlation analysis was further used to explore the association between gut microbiota and serum metabolites. PRG significantly improved gut dysbiosis in SAMP8 mice by increasing the abundance of beneficial bacterial genera, reducing pathogenic bacteria levels, and restoring the dominance of advantageous bacterial phyla. Serum metabolomics analysis revealed that PRG intervention led to significant changes in AD-related metabolites, including phenylalanine and oxidative stress markers. Combined analysis indicated a correlation between changes in gut microbiota and serum metabolites. PRG can alleviate AD symptoms in senescence-accelerated mice by regulating gut microbiota and serum metabolites, providing scientific evidence for PRG as a potential therapeutic agent for AD. This study explores the role of gut microbiota and serum metabolites under PRG intervention in neurodegenerative diseases.