iScience (Jul 2025)

Metabolomic and microbial insights: Kai-Xin-San’s impact on Alzheimer’s disease pathology

  • Huifen Ma,
  • Zhiyang Yu,
  • Qiong Qiao,
  • Wenpan Wang,
  • Zhonghua Li,
  • Pan Wang,
  • Junying Song,
  • Xiaowei Zhang,
  • Yunfang Su,
  • Yiran Sun,
  • Zhishen Xie,
  • Zhenqiang Zhang

DOI
https://doi.org/10.1016/j.isci.2025.112817
Journal volume & issue
Vol. 28, no. 7
p. 112817

Abstract

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Summary: There has been 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 inhibited the neuroinflammation, mostly 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.

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