Porcine haemoglobin peptides attenuate hypobaric hypoxia-induced fatigue via modulating the gut-muscle axis

Porcine haemoglobin peptides (PP) exhibit remarkable antioxidant properties and anti-fatigue effects. However, their potential to alleviate fatigue by modulating gut microbiota in high-altitude environments merits further investigation. This study explored the antifatigue effects of PP in hypobaric hypoxia rats. After 10 days of oral administration of PP, rich in branched-chain amino acids, rats exhibited improved exercise endurance and reduced serum fatigue biomarkers. PP treatment ameliorated the activation of Hif-1α and the elevated expression of Atrogin-1 induced by hypoxia, mitigated the decline in slow-twitch muscle fibre count, and attenuated muscle atrophy. A multi-omics analysis revealed that PP intake reshaped the gut microbiota and elevated SCFAs. These changes were associated with enhanced protein digestion and absorption, elevated valine, leucine, and isoleucine biosynthesis, and activated mTOR signalling pathway. These changes collectively ameliorated serum energy metabolism, stimulated muscle mitochondrial biogenesis and improved hypoxic exercise performance. The findings provide a theoretical foundation for developing targeted nutritional supplements to improve high-altitude hypoxic acclimatization.