Fucoidan attenuates age-related skeletal muscle atrophy via gut microbiota-dependent tryptophan metabolic Remodeling

Age-related skeletal muscle atrophy poses significant health challenges in the elderly. The gut-muscle axis has emerged as a critical regulator of muscle homeostasis, and dietary interventions targeting gut microbiota show promise. Fucoidan, a sulfated polysaccharide from marine algae, exhibits prebiotic and anti-aging properties, but its effects on age-related skeletal muscle atrophy remain unexplored.

This study aimed to investigate whether Fucoidan attenuates skeletal muscle atrophy in naturally aged mice and to elucidate the role of gut microbiota and microbial metabolites in this process.

Eighteen-month-old aged mice were orally administered Fucoidan (400 mg/kg/day) for 12 weeks. After 12-week supplementation, muscle mass, fiber size, and glycogen storage improved, with downregulation of atrophy markers (Fbx32/MuRF1) and upregulation of MyoD1. Cohousing experiments, antibiotic-induced microbiota depletion, and in vitro human fecal fermentation were integrated to validate gut microbiota dependency and tryptophan metabolism.

Fucoidan supplementation significantly improved muscle mass, fiber size, and glycogen storage, downregulated atrophy markers (Fbx32/MuRF1), and upregulated the myogenic factor MyoD1. These effects were gut microbiota-dependent, as shown by cohousing transfer. Multi-omics analyses revealed that Fucoidan reshaped gut microbial communities and enhanced tryptophan metabolic flux, which was confirmed in microbiota-depleted models and in vitro fermentation.

Fucoidan alleviates age-related muscle atrophy by remodeling gut microbiota and promoting tryptophan metabolism, highlighting its potential as a dietary intervention for age-related skeletal muscle atrophy.