Health Benefits and Molecular Mechanisms of Urolithin A: From a Gut Microbiota-Derived Metabolite to Translational Applications.

Urolithin A (UA) is an important bioactive metabolite generated by the gut microbiota from ellagic acid and ellagitannins. In recent years, it has attracted widespread attention because of its potential value in aging intervention and the prevention and treatment of multisystem diseases. This review systematically summarizes the molecular mechanisms of UA, its effects in disease intervention, and progress in human clinical studies. Existing studies have shown that, with mitochondrial quality control as the core, UA exerts multi-target biological effects through the synergistic regulation of pathways related to inflammatory responses, oxidative stress, mitophagy, and programmed cell death. Findings from in vitro mechanistic studies and animal models suggest that UA may influence pathological processes relevant to degenerative musculoskeletal diseases, cardiovascular diseases, neurological disorders, and cancers, whereas current human clinical evidence remains preliminary and is mainly concentrated in muscle function, exercise-related outcomes, selected metabolic biomarkers, and short- to medium-term safety and tolerability. In addition, this review discusses the bioavailability of UA and its relationship with individual gut microbiota metabolic phenotypes. Future research should focus on high-quality, long-term randomized controlled trials with extended follow-up to promote the application of UA in precision nutrition and its clinical translation.