Gastrointestinal Adaptations and Plasticity in High-Altitude Deer Mice

Abstract

Organisms living at high altitudes (HA) face persistent energetic challenges due to chronic cold and hypoxia, yet the role of digestive plasticity in meeting these demands remains underexplored. In this study, we used highland and lowland deer mice (Peromyscus maniculatus) acclimated to cold hypoxia (CH) to examine structural and functional remodeling of the gastrointestinal (GI) tract in response to increased energetic demand. We hypothesized that high- altitude mice enhance energy intake and digestive capacity via both evolved traits and acclimatory plasticity. Supporting this hypothesis, high-altitude mice exhibited a delayed but substantial increase in food consumption during CH exposure (~150-194% above baseline), while low-altitude mice showed no change. Both populations increased small intestine and cecum mass under CH, but only lowlanders increased colon mass, suggesting divergent strategies in digestive investment. High-altitude mice displayed elevated brush-border digestive enzyme activity (notably aminopeptidase-N), increased villus height, and expanded intestinal surface area under CH, indicating functional enhancements in nutrient digestive and absorptive capacity. These digestive enhancements were parallelled by differences in body compositions: low-altitude mice lost significantly more fat (~426%) and lean mass (~741%) with CH acclimation, leading to significant losses in overall body mass (~1300%) under CH, while high- altitude mice maintained lean, fat and overall body mass, pointing to more efficient nutrient assimilation and energy conservation. Our histological analysis revealed region-specific remodeling in high-altitude mice, including taller villi and wider crypts in the small intestine, features associated with increased absorptive surface and intestinal epithelial turnover. While both populations exhibited plastic small intestine and cecum enlargement, only high-altitude mice demonstrated the coordinated structural and enzymatic shifts needed to meet the dual energetic demands of cold and hypoxia. Taken together, these findings demonstrate that digestive system plasticity is a critical, yet underappreciated, component of energy balance at high altitude. High-altitude deer mice integrate behavioural, structural, and enzymatic responses to preserve body conditions under extreme environmental stress, offering a comprehensive model of physiological adaptation in high-altitude mammals.