A novel L-β-Galactoglucan alleviates physical fatigue by modulating load-specific metabolic pathways via the...

Prolonged physical fatigue impairs physiological homeostasis and quality of life, necessitating effective interventions. This study aimed to investigate the anti-fatigue effects and underlying mechanisms of a novel L-β-galactoglucan (APG) with two distinct molecular weights in mice under two different swimming load models using multiomics approaches. The results showed that APG could significantly extend exhaustive swimming time, reduce elevated serum lactate and blood urea nitrogen levels, increase muscle glycogen storage, and mitigate swimming-induced skeletal muscle and mitochondrial damage. Compared with its medium-molecular-weight counterpart, high-molecular-weight APG was more effective at improving these indicators. APG optimized the gut microbiota and increased the content of short-chain fatty acids. Specifically, it increased the ratio of Bacteroidetes/Bacillota and promoted the abundance of beneficial bacteria, including Dubosiella, Lachnospiraceae_UCG-006, Parabacteroides, Roseburia, Faecalibaculum and norank_o_Clostridia_vadinBB60_group, while increasing the concentrations of acetic, propanoic, and isobutyric acids. Notably, APG exerted load-specific regulatory effects: In the weight-bearing model, APG modulated mainly purine metabolism, whereas in the non-weight-bearing model, it predominantly regulated tryptophan metabolism. Both pathways converge to synergistically activate AMPK/SIRT1/PGC-1α signaling. Molecular docking further verified that APG exhibited strong binding affinity to key targets in these pathways. Collectively, these findings demonstrate that APG exerts anti-fatigue effects in a molecular weight-dependent and load-specific manner via the gut-muscle axis, providing a scientific basis for the development of APG as a targeted anti-fatigue functional ingredient.