Probiotic Bifidobacterium animalis subsp. lactis DS109-B11 ameliorates age-related muscle weakness via AMPK activation

Abstract

Abstract Sarcopenia, the age-related loss of skeletal muscle mass and function, represents a growing health burden with limited therapeutic options. Given the emerging roles of the gut–muscle axis and AMP-activated protein kinase (AMPK) in muscle homeostasis, we sought to identify gut-derived microbial strains that enhance muscle function via AMPK activation. We identified Bifidobacterium animalis subsp. lactis DS109-B11 as a potent AMPK activator. DS109-B11 microbial culture supernatant (MCS) increased AMPK phosphorylation during C2C12 myoblast differentiation, enhanced myogenic differentiation, and mitigated dexamethasone-induced myotube atrophy in vitro. In aged mice, oral administration of live DS109-B11 improved grip strength and motor performance and increased myofiber cross-sectional area, accompanied by elevated AMPK phosphorylation, upregulated mitochondrial and oxidative phosphorylation genes, and downregulated atrophy- and inflammation-related genes in skeletal muscle. In a botulinum toxin–induced neurogenic atrophy model, DS109-B11 treatment partially preserved tibialis anterior muscle mass, improved myofiber cross-sectional area, and suppressed atrophy-related gene expression. These findings identify DS109-B11 as an AMPK-activating probiotic strain that beneficially modulates skeletal muscle differentiation, enhances resilience to catabolic stress, and improves muscle function in vivo.