UC San Diego

High altitude and the hypobaric hypoxia associated with it impose significant physiological stressors on the human body. The human response to hypoxia varies between and within populations of differing genetic ancestries. This variation provides a natural experiment where potential mechanisms of hypoxia response can be investigated, especially for groups that have adapted to high altitude. This dissertation investigates the human response to hypoxia and high altitude by studying distinct populations through various biological approaches. The first chapter combines genetics, proteomics, and metabolomics data from Andean highlanders into a multi-omics analysis to predict phenotypes related to high-altitude adaptation, such as basic physiological traits, hematological traits, metabolism, and ventilation. The analysis identifies key contributors from each of the different -omics to various phenotypes. The second chapter characterizes the hypoxic ventilatory response in Tibetan women residing at high altitude and identifies an association between menopausal status and ventilation. The study further identifies genetic associations with ventilatory traits and genes under positive selection that may play a role in control of breathing. The third chapter is the results of a randomized, double-blinded, placebo-controlled study testing the effect of the probiotic SLAB51 on sea-level residents acclimatizing to high altitude. The study shows individuals that ingest the probiotic have a higher oxygen saturation and less symptoms of Acute Mountain Sickness at high altitude than those that receive a placebo. Taken together, this dissertation provides novel insights into how humans adapt and acclimatize to high altitude.