Deciphering the Therapeutic Efficacy and Underlying Mechanisms of Dendrobium officinale Polysaccharides in the Intervention of Alzheimer’s Disease Mice: Insights from Metabolomics and Microbiome

polysaccharide (DOP) has garnered attention as a potential prebiotic for its protective effects on gut microbiota and the nervous system. However, the underlying mechanism by which DOP improves cognitive dysfunction in Alzheimer's disease (AD) remains unclear. This study intends to elucidate the beneficial effects of DOP on AD mice from the perspectives of metabolomics and the intestinal microbiome. The results showed that DOP significantly ameliorated cognitive dysfunction, attenuated hippocampal neuronal damage and Aβ plaque deposition, and restored intestinal barrier integrity in AD mice. The antibiotic-cocktail-induced germ-free mouse model confirmed that the neuroprotective effect of DOP was dependent on gut microbiota. Further investigations demonstrated that DOP influenced the composition of gut microbiota and restored its diversity. Additionally, DOP reshaped metabolic profile disorders in AD mice and increased the short-chain fatty acids (SCFAs) content. Correlation analysis further highlighted that specific gut microbiota was associated with the metabolism of AD mice. In conclusion, this study sheds light on the positive impact of DOP in reshaping the gut microbiota and enhancing cognitive function, offering important perspectives for the possible advancement and utilization of DOP.