The gut microbiome contributes to adaptive thermogenesis in high-altitude deer mice (Peromyscus maniculatus)

Abstract

High altitude is one of the most extreme environments inhabited by endotherms, where extreme cold temperatures and low O2 availability (hypoxia) can constrain aerobic heat production (thermogenesis) to maintain body temperature (Tb). Recent findings suggest that the gut microbiome contributes to whole-body thermogenesis, but the significance of this mechanism for coping in cold environments is unknown. We examined whether the gut microbiome contributes to adaptive variation in thermogenic performance in deer mice at high altitude. Mice from populations native to high altitude and low altitude were born and raised in common conditions. Adults from both populations were acclimated to warm (25C) normoxia or cold (5C) hypoxia (~12 kPa O2 for 6 weeks) in a full factorial design, and a subset of mice in each group were treated with antibiotics to deplete the gut microbiome. Thermogenic endurance was then measured as the duration that Tb and metabolism could be maintained during acute cold challenge. In lowlanders, antibiotics had only modest effects on thermogenic endurance. In highlanders, in stark contrast, antibiotic treatment led to pronounced reductions in thermogenic endurance in both environments. These effects could not be explained by impairments in aerobic heat production by host thermogenic tissues, because antibiotic treatment had no effects on cold-induced increases in O2 consumption or UCP1 content of brown adipose tissue. These results suggest that the gut microbiome plays an increased role in thermogenesis in high-altitude mice. Thermogenic performance contributes to fitness at high altitude, suggesting that changes in host-microbe interactions contribute to high-altitude adaptation.