Enterococcus faecalis SI-FC-01 enhances the stress resistance and healthspan of C. elegans via AKT signaling pathway.

The global demographic is witnessing an unprecedented surge in aging, precipitating a dramatic rise in geriatric diseases and related health complications. Although probiotics have been extensively shown to maintain microbiome stability and confer health benefits, their potential role in decelerating the aging process remains largely unexplored. The study identified a beneficial gut microbe from human intestinal tract, Enterococcus faecalis SI-FC-01, which was proved to be biosafe and found to enhance the average lifespan of C. elegans by 33.55%. More interestingly, the E. faecalis SI-FC-01 also enhanced the motor ability, memory and learning ability and anti-oxidative stress ability of C. elegans. Moreover, it exhibited neuroprotective effects in the worm models of neurodegenerative diseases such as Parkinson's disease and Huntington's disease. Through screening various aging-associated mutants of C. elegans, we discovered that E. faecalis SI-FC-01 modulates DAF-16/FOXO signaling via the activation of AKT pathway. This activation subsequently triggers stress resistance and immune-related genes downstream of daf-16, thereby promoting healthspan and neuroprotection. In summary, our research indicates that E. faecalis SI-FC-01 holds significant potential as a dietary supplement for delaying host aging. Furthermore, it provides novel insights for potentially mitigating the progression of age-related neurodegenerative diseases.