Probiotic-Derived Extracellular Vesicles Attenuate Sarcopenia via Muscle Regeneration

Abstract

Postbiotic extracellular vesicles (EVs) secreted by lactic acid bacteria (LAB) have emerged as bioactive components with therapeutic potential. However, their efficacy in mitigating muscle atrophy remains unexplored. This study investigated the muscle-protective effects of postbiotic EVs derived from the probiotic Lentilactobacillus kefiri DH5 (DH5-EVs) in both palmitic acid (PA)-induced muscle atrophy in C2C12 cells and a hindlimb immobilization (HI) mouse model of sarcopenia. Biochemical characterization confirmed that DH5-EVs exhibited typical features of bacterial EVs, including protein bands in the 40–50 kDa range and a negative zeta potential. Proteomic analysis identified functional proteins such as GAPDH, arginine deiminase, and surface-layer protein with CBS domains, which are implicated in anti-inflammatory signaling and metabolic regulation. DH5-EVs significantly restored myotube integrity and upregulated Igf-1 expression in PA-treated cells. In HI mice, DH5-EV administration significantly improved grip strength, increased muscle mass, elevated MyoD expression, and reduced Atrogin-1 gene expression, with effects comparable to those of creatine administration. These findings suggest that DH5-derived EVs enhance muscle regeneration and function, offering a promising postbiotic strategy for muscle health. Moreover, these work provides mechanistic insights and supports the development of EV-based interventions for sarcopenia. © 2025 Elsevier B.V., All rights reserved.