Abstract:Hypoxia at high altitude is an important environmental factor influencing human metabolism and disease patterns. Recent epidemiological studies have shown that the prevalence of gallbladder stones is significantly higher in high-altitude regions than in low-altitude areas, yet the underlying mechanisms remain incompletely understood. Emerging evidence suggests that high-altitude hypoxia may promote gallstone formation through multiple pathways, including alterations in hepatic lipid and cholesterol metabolism, changes in bile composition, impairment of gallbladder contractility, disruption of gut microbiota homeostasis, and activation of inflammatory responses. In addition, hypoxia-induced oxidative stress, DNA damage, and epigenetic regulation may further contribute to lithogenesis. Genetic adaptation to hypoxia, such as polymorphisms in EPAS1 and related genes, may also influence individual susceptibility to gallstone disease among high-altitude populations. This review summarizes current research progress on the relationship between high-altitude hypoxia and gallbladder stones, focusing on potential mechanisms involving metabolic regulation, gallbladder motility, gut microbiota alterations, and inflammatory-epigenetic pathways, with the aim of providing insights for prevention and future research on gallstone disease in high-altitude regions.