Rhizoma Gastrodiae Water Extract Modulates the Gut Microbiota and Pathological Changes of P-Tau(Thr231) to Protect Against Cognitive Impairment in Mice

Gastrodiae Rhizoma and its active constituents are known to exhibit neuroprotective effects in Alzheimer’s disease (AD). However, the effect of Rhizoma Gastrodiae water extract (WERG) on AD and the detailed mechanism of action remain unclear. In this study, the mechanism of action of WERG was investigated by the microbiome–gut–brain axis using a D-galactose (D-gal)/AlCl(3)-induced AD mouse model. WERG improved the cognitive impairment of D-gal/AlCl(3)-induced mice. The expression level of p-Tau(thr231) in the WERG-H treatment group was decreased, and p-Tau(thr231) was found negative in hippocampal DG, CA1, and CA3 regions. Here, the diversity and composition of the gut microbiota were analyzed by 16sRNA sequencing. WERG-H treatment had a positive correlation with Firmicutes, Bacilli, Lactobacillus johnsonii, Lactobacillus murinus, and Lactobacillus reuteri. Interestingly, the Rikenellaceae-RC9 gut group in the gut increased in D-gal/AlCl(3)-induced mice, but the increased L. johnsonii, L. murinus, and L. reuteri reversed this process. This may be a potential mechanistic link between gut microbiota dysbiosis and P-Tau(Thr231) levels in AD progression. In conclusion, this study demonstrated that WERG improved the cognitive impairment of the AD mouse model by enriching gut probiotics and reducing P-Tau(Thr231) levels.