Effects and Molecular Mechanisms of Heat-Killed Postbiotic Enterococcus faecalis EF-2001 on Muscle Volume and Grip...

The interaction between the gut microbiota and human health has gained increasing recognition, accelerating advances in microbiome research. While early studies have emphasized probiotics, concerns regarding antibiotic resistance and adverse effects, such as sepsis, have shifted research interest towards heat-treated microbial cells or postbiotics. This study investigated the therapeutic potential of heat-killed postbiotic Enterococcus faecalis EF-2001-one of the most widely used postbiotics worldwide-for the prevention and treatment of muscle atrophy. In vitro, mouse C2C12 myotubes were pretreated with heat-killed postbiotic EF-2001 (50-500 μg/mL) for 48 h and then treated with dexamethasone (100 μM) to induce muscle atrophy. In vivo, male Sprague Dawley rats were treated with low-dose (3 mg/kg) and high-dose (30 mg/kg) EF-2001 for efficacy studies. Heat-killed postbiotic EF-2001 attenuated cellular and DNA damage in dexamethasone-induced C2C12 myotubes. Specifically, heat-killed postbiotic EF-2001 increased AKT phosphorylation while suppressing Atrogin-1 expression, thereby alleviating muscle atrophy. In a Sprague Dawley rat model, heat-killed postbiotic EF-2001 significantly reduced dexamethasone-induced muscle loss by regulating muscle atrophy-associated signaling pathways, including Atrogin-1 expression. Collectively, these findings demonstrate that heat-killed EF-2001 alleviates dexamethasone-induced muscle atrophy and support its potential as a postbiotic. This study provides a solid foundation for future human clinical studies by establishing preclinical evidence for the biological activity of heat-killed EF-2001.