Altitudinal variation of the gut microbiota in wild house mice

The maintenance of oxygen homeostasis in the gut is critical for the maintenance of a healthy gut microbiota. However, few studies have explored how the concentration of atmospheric oxygen affects the gut microbiota in natural populations. High-altitude environments provide an opportunity to study the potential effects of atmospheric oxygen on the composition and function of the gut microbiota. Here, we characterized the caecal microbial communities of wild house mice (Mus musculus domesticus) in two independent altitudinal transects, one in Ecuador and one in Bolivia, from sea level to nearly 4,000 m. First, we found that differences in altitude were associated with differences in the gut microbial community after controlling for the effects of body mass, diet, reproductive status and population of origin. Second, obligate anaerobes tended to show a positive correlation with altitude, while all other microbes tended to show a negative correlation with altitude. These patterns were seen independently in both transects, consistent with the expected effects of atmospheric oxygen on gut microbes. Prevotella was the most-enriched genus at high elevations in both transects, consistent with observations in high-altitude populations of pikas, ruminants and humans, and also consistent with observations of laboratory mice exposed to hypoxic conditions. Lastly, the renin–angiotensin system, a recently proposed microbiota-mediated pathway of blood pressure regulation, was the top predicted metagenomic pathway enriched in high altitudes in both transects. These results suggest that high-altitude environments affect the composition and function of the gut microbiota in wild mammals.