전지현 (서울대학교)

이도엽 (서울대학교)

전지현 (서울대학교)

장지훈 (고려대학교)

오남수 (고려대학교)

이도엽 (서울대학교)

 Sarcopenia, the age-related loss of muscle mass and function, poses a significant health burden but still lacks effective treatments. Here, we investigated fermented whey protein isolate (F-WPI) as a potential therapeutic and explored its mechanism through microbiome and metabolomic analyses.

 Sarcopenia was induced in C57BL/6 mice via hindlimb immobilization, followed by treatment with F-WPI, WPI, or the fermentation strain (IM13). We performed 16S rRNA sequencing on feces and LC-MS-based metabolomic profiling on feces, serum, and gastrocnemius muscle.

 F-WPI treatment led to the most significant recovery of grip strength, muscle mass, and fiber size. Notably, this phenotypic improvement was accompanied by a restoration of gut microbiota composition to a state resembling that of normal mice. This microbial shift strongly correlated with changes in gut and muscle metabolites. Specifically, F-WPI-treated mice showed increased muscular acylcarnitines and fatty acids, suggesting enhanced energy metabolism. Network analysis revealed key associations between improved muscle phenotype, microbial taxa, gut metabolites, and muscle metabolites.

 In conclusion, our integrated multi-omics approach demonstrates that F-WPI alleviates sarcopenia by remodeling the gut microbiome, which in turn modulates systemic metabolism to enhance muscle function. This study provides a novel insight into the gut-muscle axis and supports F-WPI as a promising microbiome-targeted nutritional strategy.