Li Wenhao, Wang Yuhao, Shi Yi, He Fenfen, Zhao Zaihua, Liu Jingchun, Gao Zhenbo, Zhang Jianbin, Shen Xuefeng
Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an, China.
School of Public Health, Shaanxi University of Traditional Chinese Medicine, Xianyang, China.
FEBS J. 2025 Feb;292(4):809-826. doi: 10.1111/febs.17365. Epub 2024 Dec 23.
Hypoxia is a predominant risk factor at high altitudes, and evidence suggests that high-altitude hypoxia alters the gut microbiota, which plays an essential regulatory role in memory function. However, the causal relationship between the gut microbiota and memory impairment under hypoxic conditions remains unclear. In this study, we employed a high-altitude hypoxia model combined with fecal microbiota transplantation (FMT) approach in mice to explore the effects of the gut microbiota on memory impairment in a hypoxic environment. We observed that high-altitude hypoxia exposure reduced short- and long-term memory and hippocampus-dependent fear memory abilities, along with decreased relative abundance of Ligilactobacillus and Muribaculum. Moreover, hypoxic conditions increased intestinal and blood-brain barrier permeability. FMT from hypoxia-exposed mice into naïve antibiotic-treated mice resulted in similar memory impairments, Ligilactobacillus and Muribaculum abundance changes, and increased intestinal/blood-brain barrier permeability. Correlation analysis showed a robust positive association between Ligilactobacillus and Muribaculum with hippocampus-dependent contextual fear memory. Likewise, Ligilactobacillus was positively correlated with short-term memory. Therefore, Ligilactobacillus and Muribaculum may be key microbes in reducing memory ability in hypoxia, with the intestinal and blood-brain barriers as primary pathways. Our findings provide further evidence for the potential regulatory mechanism by which gut microbiota dysbiosis may contribute to memory impairment in a high-altitude environment.
缺氧是高海拔地区的主要风险因素，有证据表明高海拔缺氧会改变肠道微生物群，而肠道微生物群在记忆功能中起着至关重要的调节作用。然而，缺氧条件下肠道微生物群与记忆障碍之间的因果关系仍不清楚。在本研究中，我们采用高海拔缺氧模型结合粪便微生物群移植（FMT）方法在小鼠中探索肠道微生物群对缺氧环境下记忆障碍的影响。我们观察到，高海拔缺氧暴露降低了短期和长期记忆以及海马体依赖性恐惧记忆能力，同时降低了Ligilactobacillus和Muribaculum的相对丰度。此外，缺氧条件增加了肠道和血脑屏障的通透性。将缺氧暴露小鼠的粪便微生物群移植到经抗生素处理的未接触过缺氧的小鼠中，导致了类似的记忆障碍、Ligilactobacillus和Muribaculum丰度变化以及肠道/血脑屏障通透性增加。相关性分析显示，Ligilactobacillus和Muribaculum与海马体依赖性情境恐惧记忆之间存在强烈的正相关。同样，Ligilactobacillus与短期记忆呈正相关。因此，Ligilactobacillus和Muribaculum可能是缺氧条件下降低记忆能力的关键微生物，肠道和血脑屏障是主要途径。我们的研究结果为肠道微生物群失调可能导致高海拔环境下记忆障碍的潜在调节机制提供了进一步的证据。
