In-depth investigation of the mechanisms of Schisandra chinensis polysaccharide mitigating Alzheimer's disease rat via gut microbiota and feces metabolomics

Schisandra chinensis (S. chinensis) is an herbal medicine used for the treatment of Alzheimer's disease (AD). The purified polysaccharide fraction, namely SCP2, was previously isolated from S. chinensis crude polysaccharide (SCP) and its structure and in vitro activity were investigated. However, the in vivo activity of SCP2 and its potential mechanism for the treatment of AD have yet to be determined. This study used a combination of microbiomics and metabolomics to comprehensively explore the microbiota and metabolic changes in AD rats under SCP2 intervention, with the aim of elucidating the potential mechanisms of SCP2 in the treatment of AD. SCP2 showed significant therapeutic effects in AD rats, as evidenced by improved learning and memory capacity, reduced neuroinflammation, and restoration of the integrity of the intestinal barrier. Fecal metabolomic and microbiomic analyses revealed that SCP2 significantly modulated 19 endogenous metabolites and reversed gut microbiota disorders in AD rats. Moreover, SCP2 significantly increased the content of short-chain fatty acid (SCFAs) in the AD rats. Correlation analysis showed a significant correlation between gut microbes, metabolites and the content of SCFAs. Collectively, these findings will provide the basis for further development of SCP2.