Baicalein-corrected gut microbiota may underlie the amelioration of memory and cognitive deficits in APP/PS1 mice

Background: Baicalein is an active ingredient extracted from the root of S. baicalensis Georgi, which exhibits cardiovascular protection, anti-inflammatory, and anti-microbial properties. Our previous study showed that chronic treatment of Baicalein ameliorated cognitive dysfunction in a mouse model of Alzheimer's disease (AD). However, it remains unknown whether Baicalein ameliorates cognitive deficits in AD mouse models by altering gut microbiota and its metabolites. Methods: Behavioral tests, metagenomic and untargeted metabolomics analyses were used to evaluate the effects of Baicalein on the APP/PS1 mice. Results: Our research showed that treatment of Baicalein for 2 weeks ameliorated cognition and memory in a dose-dependent manner, as indicated by the significant increases in the Discrimination index and Number of crossings and decrease in latency to the previous platform location in 8-month of age APP/PS1 mice in novel object recognition and water maze tests. The metagenomic analysis showed the abundance of the dominant phyla in all groups, including Bacteroidetes (14.59%–67.02%) and Firmicutes (20.19%–61.39%). LEfSe analysis of metagenomics identified three species such as s__Roseburia_sp_1XD42_69, s__Muribaculaceae_bacterium_Isolate_104_HZI, s__Muribaculaceae_bacterium_Isolate_110_HZI as Baicalein-treated potential biomarkers. Metabolite analysis revealed the increment of metabolites, including glutamate, thymine and hexanoyl-CoA. Conclusion: The effects of Baicalein on memory and cognition may relate to the metabolism of nucleotides, lipids and glucose.