Abstract
BACKGROUND: Recent studies focus on the genetic and physiological characteristics of the plains Han, plateau Han, and Tibetan populations. However, systematic studies on the differences in metabolic and microbial communities in high-altitude environments remain limited. RESULTS: This study profiled metabolomes and microbiomes in plain Han, plateau Han, and Tibetan populations. Differential analysis revealed 30 metabolites and notable alterations in microbial community composition between plain Han and plateau Han. Prevotella, Streptococcus, and Ruminococcus, mainly participating in purine metabolism, were enriched in the plateau Han population. Bacteroidota and Firmicutes were the primary differential bacterial phyla indicating adaptive alternatives, particularly in steroid metabolism. Thirty-four distinct metabolites were identified between plateau Han and Tibetan individuals, including significant lipids such as ceramide, triglycerides (TG), and phosphatidylethanolamine (PE). These lipids and metabolites were integrally involved in energy metabolism and inflammatory pathways, highlighting the importance of high-altitude environments for metabolic health. CONCLUSIONS: This study identified significant associations between metabolic, lipid, and microbial differences and altitude-induced physiological variation, illustrating population adaptations to extreme environments. Our systematic comparative analysis improves our understanding of high-altitude adaptability, underlining the importance of integrating metabolic and microbiological analyses and facilitating future research on associated disorders.