The role of the gut microbiota-uric acid metabolism axis in high-altitude hyperuricemia: dysregulation mechanisms, pathway associations and therapeutic perspectives.

High-altitude areas (≥2500 m) are characterized by low oxygen concentrations, which leads more people affected by high uronic acid in the blood. This review systematically investigates the "gut microbiota-uric acid metabolism axis" as a potential target for inhibiting Hyperuricemia (HUA). This review introduces the four functions of the axis: direct reduction of uric acid, intestinal excretion, regulation of uricase expression, and the intestinal-renal axis signal; then investigates how hypoxia alters all of these paths. In addition, this review illustrates how this axis is related to the classical metabolic pathway of purine synthesis, renal excretion, lactate metabolism, inflammatory-oxidative stress and genetic susceptibility. Adaptation difference: Native highlanders and migrants show different degrees of adjustment to life in the mountains, and migrants are relatively more prone to axis dysfunction. Finally, this review introduces targeted intervention strategies, such as probiotics, prebiotics, fecal microbiota transplantation, and their combination with uric acid-lowering or anti-inflammatory drugs, and put forward a population-stratified precision intervention framework. Overall, this paper provides a theoretical foundation and novel direction for understanding and preventing plateau HUA.