Metabolomic and Microbial Insights: Kai-Xin-San's Impact on Alzheimer's Disease Pathology

An increasing interest in the connection between AD, gut microbiota, and metabolites. Kai-Xin-San (KXS) has been commonly employed in ancient and modern Chinese clinical trials for the treatment of dementia; however, whether the protective effect of KXS in AD is related to the gut microbiota remains elusive. APP/PS1 mice were used as the model of AD. 43 key metabolites influenced by KXS were screened using untargeted metabolomics. At the genus level, Clostridium_IV, Eubacterium, Acetatifactor, etc were identified to be impacted by KXS using 16S rRNA sequencing. Additionally, we identified 9 distinct intestinal floras at the genus level that were correlated with 13 pivotal differential metabolites related to cognitive impairment. KXS also markedly inhibited the neuroinflammation, may via regulating the key metabolites. A potential relationship between gut microbiota, metabolites, and neuroinflammation is suggested as a protective mechanism of KXS in AD. These findings provide support for further development of KXS.

学界对阿尔茨海默病（Alzheimer's Disease, AD）、肠道菌群（gut microbiota）与代谢物之间的关联关注度与日俱增。开心散（Kai-Xin-San, KXS）在古今中医药临床研究中被广泛用于痴呆的治疗，但其对阿尔茨海默病的保护作用是否与肠道菌群相关，目前仍不明晰。本研究以APP/PS1小鼠作为阿尔茨海默病模型，通过非靶向代谢组学（untargeted metabolomics）技术筛选出43种受开心散调控的关键代谢物；采用16S rRNA测序（16S rRNA sequencing）技术，在属水平上鉴定出梭菌属IV（Clostridium_IV）、真杆菌属（Eubacterium）、嗜乙酰杆菌属（Acetatifactor）等受开心散调控的菌群。此外，本研究在属水平上鉴定出9种独特肠道菌群，它们与13种与认知功能障碍相关的关键差异代谢物存在关联。开心散还可显著抑制神经炎症，其作用机制可能与调控上述关键代谢物有关。本研究提示肠道菌群、代谢物与神经炎症之间的潜在关联，可作为开心散发挥阿尔茨海默病保护作用的潜在机制；上述研究结果为开心散的后续开发提供了有力支撑。