Short-Term High-Altitude Exposure Alters Pharyngeal and Gut Microbiome

High-altitude exposure poses significant health challenges, where microbial communities may serve as important contributors to host acclimatization. We conducted a longitudinal study to investigate the dynamic changes in pharyngeal and gut microbiota before, during, and after acclimatization to the Mount Qomolangma region (high-altitude, 4300–5200 m above sea level, m.a.s.l.). Twenty healthy participants underwent four health visits: at baseline level (Beijing, 50 m.a.s.l.), upon arrival at the high altitude, after a week of acclimatization, and upon return to the baseline level. Throat swabs and fecal samples were collected for 16S rRNA amplicon sequencing to assess microbial composition and diversity. Linear mixed-effects models were employed to estimate the altitude-associated variations in pharyngeal and gut microbes compared to the baseline. Pharyngeal microbial diversity showed statistically significant alterations after 1 week at high altitude, with the Shannon index decreasing by 12.0% (95% CI: −21.8 to −2.9%) and the Simpson index increasing by 2.6% (1.3 to 4.0%). In contrast, gut microbial diversity decreased upon initial high-altitude exposure but tended to revert to baseline after 1 week of acclimatization. Beta diversity analyses revealed significant differences in pharyngeal microbiota across visits, while gut microbiota differences were less pronounced. Using the linear discriminant analysis effect size (LEfSe) method, we identified 11 pharyngeal and four gut microbes that were differentially abundant across visits, which could shape the host’s resilience to high-altitude challenges. Our study reveals that high-altitude exposure disrupts pharyngeal and gut microbial diversity over time and modulates the abundance of some opportunistic pathogens. These shifts may mediate host responses to hypoxic environments, underscoring the microbiomes’ role in physiological acclimatization.