Protective Effects of Limosilactobacillus fermentum EFEL6800 on Muscle Atrophy: Insights from Gut Microbiota Modulation and Bioactive Metabolite Production

• This study demonstrates that Limosilactobacillus fermentum EFEL6800 (LBF6800) protects against muscle atrophy in dexamethasone-induced C2C12 cells and mice. • LBF6800 reduced muscle atrophy markers and improved muscle function by promoting muscle synthesis and inhibiting protein degradation. • It also modulated gut microbiota, enhancing beneficial bacteria and acetate production. • The whole genome analysis confirmed the strain's probiotic stability and safety, indicating that LBF6800 is considered safe for use and regarded as a functional probiotic candidate for improving muscle health. Pathological conditions such as muscle atrophy and sarcopenia are characterized by reductions in skeletal muscle mass and strength, leading to impaired physical function. This study investigates the protective effects of Limosilactobacillus fermentum EFEL6800 in dexamethasone (DEX)-induced C2C12 cells and murine model by evaluating their impact on gut microbiota and bioactive metabolite production. To investigate the protective effects of LBF6800, in vitro and in vivo experiments were conducted using DEX-induced C2C12 cells and a mouse model. In addition, the whole genome analysis of LBF6800 was performed. As a result, the cell culture and lysate supernatant of LBF6800 reduced muscle atrophy markers and increased muscle synthesis markers in DEX-induced C2C12 myotubes. In the DEX-induced mouse model, LBF6800 treatment significantly improved grip strength by 15.33% and attenuated the reduction in cross-sectional area of gastrocnemius muscle fibers (32.09 μm²) compared to the DEX-treated group (29.79 μm²) by inhibiting protein degradation pathways and promoting muscle-specific markers such as myosin heavy chains. Additionally, LBF6800 supplementation induced beneficial alterations in the gut microbiota, increasing the abundance of health-promoting bacteria such as Lactobacillus reuteri (9.26%), Bifidobacterium choerinum (17.35%), and Faecalibaculum (17.31%) compared to the control group (0.33, 3.58, and 6.68%, respectively), and significantly enhanced acetate production from 1,661 ± 321 µM to 1,844 ± 240 µM, whereas the control group showed a decrease from 1,902 ± 303 µM to 1,249 ± 195 µM. The whole genome analysis demonstrated the absence of antibiotic resistance or toxin gene transfer potential, along with genes related to probiotic stability and functionality. These findings suggest that LBF6800 has promising potential as a probiotic intervention for preventing muscle atrophy and sarcopenia, with possible applications in dietary supplementation or functional foods for aging populations. This graphic scheme presented the protective effects of Limosilactobacillus fermentum EFEL6800 on dexamethasone (DEX)-induced muscle atrophy in mice.