Altitude adaptation: The unseen work of gut microbiota

High altitudes are one type of extreme environment characterized by hypobaric hypoxia, extreme cold, strong ultraviolet radiation, and low energy availabilty that present tremendous challenges to human and wildlife inhabiting these environs. These extreme environments serve as a unique natural laboratory for delving into the impact of selective pressures on species variation and adaptation. This narrative review compiles the latest research on high-altitude adaptation, with a specific focus on the crucial role of gut microbiota in this process. Evidence indicates that gut microbiota significantly impacts an organism's ability to adapt to high-altitude conditions by adjusting its composition, and hence impacting its function and ability to release microbial metabolites. We explore the link between gut microbiota and high-altitude environments, the microbial signatures, and their effects on adaptation, as well as the potential for targeted modulation of gut microbiota to enhance acclimatization to high altitudes. By examining the interaction between microbiota and host adaptation, this review aims to promote further mechanistic studies and support strategies for improving high-altitude acclimatization through gut microbiota modulation. Different durations of high-altitude exposure evoke dynamic alteration of gut microbiota. There are overlapped signatures of alteration in gut microbiota among plateau indigenous mammals. Gut microbiota bidirectionally impacts highland adaptation via its metabolites. Targeted modulation of gut microbiota promotes highland acclimation. • Different durations of high-altitude exposure evoke dynamic alteration of gut microbiota. • There are overlapped signatures of alteration in gut microbiota among plateau mammals. • Gut microbiota bidirectionally impacts highland adaptation via its metabolites. • Targeted modulation of gut microbiota promotes highland acclimation.