Conclusion

In conclusion, this study identified three serum metabolites independently associated with MVV in native high‑altitude Tibetans through a standardized multi‑stage metabolomic screening and validation strategy. Further sensitivity analysis confirmed that the core metabolic signatures linked to ventilatory function were robust and not dependent on exogenous drug‑derived metabolites, supporting the reliability of the present findings. These results provide preliminary metabolic evidence for individual differences in pulmonary ventilatory adaptation under chronic high‑altitude hypoxia.

The metabolite‑based model presented moderate predictive performance and screening stability, which likely reflects the multifactorial and weakly regulated nature of pulmonary function in plateau populations. Owing to the limited number of candidate metabolites, pathway enrichment analysis was not feasible in this study. Despite inherent limitations including a moderate sample size, single‑center cross‑sectional design, and incomplete medication information, this work offers potential metabolic biomarkers for evaluating high‑altitude respiratory adaptation.

Future large‑scale prospective cohorts and functional experiments are needed to validate the causal relationships between key metabolites and hypoxic pulmonary adaptation and further elucidate the metabolic regulatory mechanisms underlying high‑altitude respiratory physiological phenotypes.