Effects of acute severe hypobaric hypoxia on gut-muscle axis in rats

Acute exposure to high-altitude hypobaric hypoxia (HH) disrupts physiological homeostasis. While gastrointestinal and neurological disturbances are its main manifestations, muscle function is also affected. However, its short-term effects on the gut-muscle axis remain poorly understood. The present study investigated the impact of a 4-hour exposure to simulated altitude (5,000 m) on intestinal morphology, gut microbiota composition, short-chain fatty acid (SCFA) levels, and skeletal muscle mitochondrial function in male Sprague-Dawley rats. Despite the severity of the hypoxic stimulus, biometric and hematological parameters remained largely unchanged, suggesting preserved systemic stability. Histological analysis revealed a significant reduction in intestinal crypt depth, indicating early structural alterations, while villus morphology and goblet cell counts remained unchanged. Microbiota profiling showed a decrease in Enterobacteriales abundance, while other bacterial groups and SCFA concentrations remained stable, pointing to limited microbial shifts under acute conditions. In skeletal muscle, reactive oxygen species (ROS) production increased under complex I-supported respiration while mitochondrial respiration was maintained across all respiratory states. This suggests a qualitative shift in redox balance. Collectively, these findings indicate that acute HH triggers early localized responses in intestinal and muscular tissues without inducing widespread systemic disruption, highlighting the resilience of the gut-muscle axis to short-term hypoxic stress. Longer or repeated exposures may be required to elicit broader physiological adaptations. This study contributes to understanding the early effects of altitude-related hypoxia and underscore the importance of exposure duration in shaping host responses.