Gut microbiota's role in high-altitude cognitive impairment:the therapeutic potential of Clostridium sp.supplementation  

作　　者：Wei Zhou Yongqiang Zhou Shikun Zhang Bin Li Zhong Li Zhijie Bai Dezhi Sun Chaoji Huangfu Ningning Wang Tiantian Xia Congshu Huang Lina Guan Xi Yang Yangyi Hu Pengfei Zhang Pan Shen Rui Wang Zhexin Ni Yue Gao 

机构地区：[1]Department of Pharmaceutical Sciences,Beijing Institute of Radiation Medicine,Beijing,100850,China [2]Department of Stem Cell and Regenerative Medicine,Institute of Health Service and Transfusion Medicine,Beijing,100850,China [3]Mountain Sickness Research Institute,No.950 Hospital,Yecheng,844900,China [4]Department of Stomatology,the First Medical Center,Chinese PLA General Hospital,Beijing,100853,China [5]Medical School of Qinghai University,Xining,810016,China [6]General Hospital of Xinjiang Military Command,Urumqi,830000,China [7]State Key Laboratory of Kidney Diseases,Chinese PLA General Hospital,Beijing,100853,China

出　　处：《Science China(Life Sciences)》2025年第4期1132-1148,共17页中国科学(生命科学英文版)

基　　金：supported by the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202207,Y.G.);the Young Elite Scientists Sponsorship Program by CAST(2021-QNRC1-03,W.Z.)。

摘　　要：Prolonged exposure to high-altitude environments may increase the risk of cognitive decline in young migrants.Recent studies suggest that hypobaric hypoxia-induced alterations in gut microbial composition could partly contribute to this risk.However,the absence of direct evidence from cohort studies and an unclear mechanism hinder intervention development based on this hypothesis.This study recruited109 young male migrants living in Xizang to investigate the microbial mechanisms underlying cognitive impairment associated with highaltitude migration.Multi-omic analysis revealed distinct microbiome and metabolome features in migrants with cognitive decline,notably a reduced abundance of Clostridium species and disrupted fecal absorption of L-valine.Mechanistic studies showed that hypobaric hypoxia significantly damaged the intestinal barrier,leading to lipopolysaccharide(LPS)leakage and an influx of inflammatory factors into the peripheral blood,which activated microglia and caused neuronal injury in the hippocampus of mice.Additionally,compromised L-valine absorption due to intestinal barrier damage correlated with lower hippocampal glutamate levels and neurotrophic factors.Intervention with Clostridium sp.effectively restored the intestinal barrier and enhanced L-valine absorption,which mitigated hypobaric hypoxiainduced inflammation and hippocampal neural damage in mice.In conclusion,cognitive impairment among young migrants at high altitude may be attributed to hypobaric hypoxia-induced gut microbiota disruption and subsequent intestinal barrier dysfunction.This study may provide a promising approach for preventing and treating high-altitude-associated cognitive impairment.

关 键 词：HIGH-ALTITUDE cognition impairment microbial mechanisms Clostridium sp. L-VALINE 

分 类 号：R57[医药卫生—消化系统]