Selenium-enriched Lacticaseibacillus rhamnosus SHA113 alleviates fatigue under simulated high-altitude hypoxia in mice through intestinal microbiota and antioxidant modulation

Exercise intolerance is a common issue upon acute exposure to high altitude when a person enters high-altitude environment before adapted. Oxidative stress and intestinal microbiota imbalance are increasingly recognized as important contributors to hypobaric hypoxia-associated fatigue. Selenium is a well-known anti-oxidative nutrient and probiotics are widely accepted as intestinal microbiota regulators. In this study, selenium-enriched Lacticaseibacillus rhamnosus SHA113 (Se-SHA113) was evaluated for its potential to alleviate exercise-related fatigue under simulated high-altitude environment (4500 m). Mice were orally administered Se-SHA113 (0.12 mg Se/kg body weight) for 4 days before hypobaric hypoxia exposure. Se-SHA113 supplementation prolonged exercise performance and was associated with an increased abundance of a taxon annotated as Lactobacillus reuteri in the intestinal microbiota. An intervention with Lactobacillus reuteri ATCC 53608 (LR; 1 × 108 CFU/day for 4 days) was also conducted. LR supplementation reproduced part of the beneficial phenotype. Both interventions improved fatigue-related biomarkers, including preservation of hepatic and muscle glycogen, enhancement of intestinal antioxidant enzyme activities, and elevation of fecal short-chain fatty acids, particularly acetate and butyrate. Reduced colonic oxidative stress was also observed after Se-SHA113 treatment. Overall, Se-SHA113 showed potential to alleviate hypobaric hypoxia-associated fatigue under simulated high-altitude environment. These effects were associated with selective intestinal microbiota remodeling, improved glycogen storage, and strengthened intestinal antioxidant defenses, supporting Se-SHA113 as a promising candidate for nutritional intervention under limited-oxygen conditions.