ABSTRACT Indigenous high-altitude populations maintain relatively normal brain function despite chronic hypoxia, yet the underlying neurophysiological mechanisms and the potential role of gut-brain interaction remain unclear. This study combined 16S rRNA gut microbiota profiling in 211 high-altitude indigenous populations at 2, 3, and 4 km altitudes with resting-state and task-based electroencephalography recordings in 135 of them. Residents at 4 km showed enhanced delta (1–4 Hz) power across most brain regions along with increased frontal-occipital functional connectivity (FC) during resting state. During a cognitive oddball task, the 4 km group exhibited elevated P3 amplitude in response to oddball stimuli, together with larger parietal delta power. In parallel, the 4 km group displayed higher species richness and an elevated abundance of short-chain fatty acid-producing genera such as Roseburia , Blautia , and Coprococcus . Furthermore, the abundance of Blautia was positively associated with resting-state FC, a relationship that may further influence anxiety and sleep quality. Our findings demonstrate a coordinated gut-brain interaction adaptation to high altitude, highlighting the homeostatic role of microbial pathways. IMPORTANCE Indigenous high-altitude populations maintain normal cognitive function under chronic hypoxia, a process potentially involving the gut microbiota. Our study added evidence that the neural activity patterns and gut microbiota structure may work in coordination to assist the host in adapting to extreme environments.
Bai et al. (Wed,) studied this question.