Phenyllactic acid modulates the gut microbiota, enhances intestinal health, and alleviates physical frailty in aging mice.

Phenyllactic acid (PLA) is a natural antibiotic-like compound derived from certain foods and probiotics. PLA levels have been associated with age-related sarcopenia and provide benefits to metabolic health when derived from probiotics. However, the specific regulatory effects of PLA in aging remain largely unexplored. In this study, aging mice were administered PLA via gavage, followed by fecal 16S rRNA sequencing, measurements of targeted metabolites, glucose metabolism monitoring, and physical performance assessments. Our results indicate that PLA administration significantly altered gut microbiota composition, increased the abundance of short-chain fatty acids (SCFAs) and succinate producing microbiota, and enhanced gut integrity in aging mice. Furthermore, PLA treatment raised fasting blood glucose levels and improved physical activity. Mechanistically, PLA intake elevated the levels of circulating SCFAs and succinate, promoting glycogen metabolic homeostasis and maintaining skeletal muscle oxidative capacity. This study provides evidence that PLA modulates the gut microbiota in aging mice, supports intestinal health, promotes glucose homeostasis, and enhances physical activity.