Integrating fecal metabolomics and gut microbiome to reveal the mechanism of Schisandra chinensis-Acorus tatarinowii Schott treatment in Alzheimer's disease rats

Background: Schisandra chinensis (Turcz.) Baill (Schisandraceae) and Acorus tatarinowii Schott (Araceae Juss) (ScAt) are two traditional Chinese medicinal herbs that are widely used in the treatment of neurological disorders such as insomnia. In our previous study, we found that Sc-At could improve the therapeutic efficacy of Alzheimer's disease by affecting aromatase activity and estrogen levels, among other pathways. Material and methods: In this study, first, the ameliorative effect of Sc-At on cognitive dysfunction in Alzheimer's disease model rats was verified by Y-maze test together with Elisa assay. Second, fecal untargeted metabolomics analysis was performed using a UPLC-Q-TOF/MS-based metabolomics approach. 16S rDNA sequencing was utilized to screen the differential flora between groups, and linear discriminantan alysis effect size (LEfSe) was used to find the target flora. Finally, Spearman correlation analysis was combined to find the relationship between differential flora and differential metabolites in feces. Results: (1) The results of Y-maze test and Elisa assay indicated that Sc-At could improve the cognitive dysfunction of AD model rats. (2) Metabolomics results showed that fecal metabolite levels were significantly different from those of rats in the blank group, and 18 potential biomarkers in feces were screened, mainly affecting linoleic acid metabolism, steroid hormone biosynthesis, sphingomyelin metabolism, riboflavin metabolism, etc. The 16S rDNA results showed that the abundance and diversity of intestinal flora in AD rats were destroyed, and the Sc-At treatment was able to reverse these changes. (3) Spearman's correlation analysis showed a significant correlation between differential metabolites in feces and intestinal flora, further suggesting that Sc-At treats Alzheimer's disease through the gut-brain axis. Conclusions: In this study, we explored the mechanism of Sc-At in the treatment of Alzheimer's disease by integrating fecal untargeted metabolomics and 16S rDNA gene sequencing, and the results showed that Sc-At exerts therapeutic effects on Alzheimer's disease by improving the intestinal flora and related metabolic pathways.