Lactobacillus plantarum WY2401 Promotes Myogenesis

Microbe-host interaction has an important influence on the development of skeletal muscle and the pathogenesis of muscle-related disorders. However, the molecular mechanisms through which microbiota-derived signals regulate host myogenic programs remain poorly understood. Here, we identify Lactobacillus plantarum WY2401 as a pro-myogenic probiotic strain that promotes skeletal muscle regeneration. Oral administration of L. plantarum WY2401 could accelerate cardiotoxin-induced muscle repair in mice, as evidenced by improved myofiber regeneration and increased expression of myogenic markers. Subsequent serum metabolomic profiling identified riboflavin as a prominently elevated circulating factor in L. plantarum WY2401-treated mice. Mechanistically, riboflavin alters the expression of the m6A methyltransferase METTL3 in a stage-dependent manner during myogenesis, promoting proliferation through a METTL3-m6A-CDK2/CCND1 axis while facilitating differentiation through a METTL3-m6A-MEF2A axis. Collectively, our findings reveal a novel microbe-host regulatory axis through which L. plantarum WY2401 enhances skeletal muscle regeneration via stage-specific epitranscriptomic regulation of myogenesis.