Ginkgo biloba Extract Drives Gut Flora and Microbial Metabolism Variation in a Mouse Model of Alzheimer’s Disease

Alzheimer’s disease (AD) is a complex neurodegenerative disease. Numerous investigations have demonstrated that medications that regulate the “brain–gut” axis can ameliorate disease symptoms of AD. Studies have shown that Ginkgo biloba extract (EGb) is involved in intestinal metabolism to meet the goal of illness treatment. EGb is currently utilized extensively in the clinical prevention and treatment of cardiovascular and cerebrovascular diseases. However, the regulatory effect of EGb on intestinal flora and its metabolites in AD pathology remains largely speculative. In this study, the Morris water maze test showed a significant improvement of spatial memory in the AD mouse model (APP/PS1 mice) after EGb treatment. We next confirmed the positive effects of EGb on the gut flora and metabolites of APP/PS1 mice and further showed that EGb treatment reshaped the disturbed gut microbiome, in particular by reducing the Firmicutes/Bacteroides ratio and increasing the abundance of Bacteroidetes, Uroviricota, Streptophyta, and Spirochaetes. Meanwhile, a non-targeted metabolomics analysis showed that EGb treatment significantly reversed the dysfunction of the microbial metabolic phenotype by altering Limosilactobacillus and Parvibacte, with 300 differential metabolites modulated (131 up-regulated, 169 down-regulated). Our findings highlight the significant regulatory impact of EGb on intestinal microflora and microbial metabolism in AD mice models and provide a potential therapeutic strategy for AD.