基于16S rDNA测序分析肠道菌群结构探讨癫痫清颗粒对阿尔茨海默病模型小鼠学习记忆的影响OA

Objective To investigate the effects of Dianxianqing Granules on learning and memory ability in P301S transgenic model mice based on 16S rDNA gut microbiota analysis.Methods Specific pathogen-free(SPF)C57BL/6 mice were used as the control group(WT group).SPF P301S transgenic mice were randomly divided into the model group(P301S group),Dianxianqing Granule group(DXQ group),and donepezil hydrochloride group(Y group).The treatment groups were intragastrically administered Dianxianqing Granules(12.48 g/kg)or donepezil hydrochloride(1.30 mg/kg),while the WT and P301S groups received an equal volume of distilled water,once daily for 5 months.Behavioral tests were conducted to evaluate learning and memory ability.Hematoxylin-eosin staining was used to observe structural changes in hippocampal neurons.Fecal samples were collected for genomic DNA extraction,followed by PCR amplification,product recovery and purification,fluorescence quantification,and sequencing.Bioinformatics methods were applied for microbiota diversity analysis,microbiota dysbiosis index analysis,species community composition analysis,and linear discriminant analysis effect size(LEfSe)analysis.Results Compared with the WT group,the P301S group showed decreased spontaneous alternation rate,prolonged latency,reduced platform crossings,decreased operational taxonomic unit(OTU)numbers,and declined Alpha diversity indices(including Sob,Chao,and Ace indices),along with increased gut microbiota dysbiosis.At the phylum level,the relative abundance of Firmicutes was significantly decreased,while Bacteroidota,Proteobacteria,and Desulfobacterota were significantly increased.At the genus level,the relative abundance of Dubosiella was reduced,whereas Escherichia-Shigella and unclassified Lachnospiraceae were increased.Abnormal changes in hippocampal neuron structure were also observed.Compared with the P301S group,the DXQ group exhibited increased spontaneous alternation rate,shortened latency,increased platform crossings,elevated OTU numbers,improved Alpha diversity,and restored microbiota abundance at both phylum and genus levels.Conclusion Dianxianqing Granules can ameliorate learning and memory impairment by increasing the abundance of Firmicutes/Dubosiella and reducing the abundance of Bacteroidota/Escherichia-Shigella,thereby improving gut microbiota dysbiosis.