The exercise-gut-muscle axis in physical frailty: A narrative review

The prevalence of physical frailty has increased in recent years, owing to an aging population. This geriatric syndrome is characterized by a decline in physiological reserve and physical function. Thus, the risk of adverse health outcomes amongst individuals in a state of frailty is high. Frailty development is strongly influenced by skeletal muscle dysfunction, which involves reductions in muscle mass, strength, and metabolic capacity. Exercise is the most effective approach for the maintenance of muscle function and prevention of functional decline in older adults. However, the biological mechanisms underlying its role in aging remain unclear. The gut microbiota produces various bioactive metabolites that affect metabolic regulation, immune responses, and inflammatory pathways. Exercise may modify the composition and metabolic function of the gut microbiota in some studies, although the findings remain inconsistent. These exercise-associated alterations may influence the production of microbial metabolites that may affect skeletal muscle metabolism. Recent evidence on age-related alterations in the gut microbiota is reviewed here, with a focus on how these changes relate to skeletal muscle physiology. Furthermore, the mechanisms by which exercise modifies the composition and metabolic pathways of the gut microbiota are described, highlighting the concept of the "exercise-gut-muscle axis" as a framework linking physical activity, the gut microbiome, skeletal muscle, and physical frailty trajectories. Our narrative synthesis integrates the emerging evidence on exercise-microbiome-muscle interactions. This may help identify priorities for future research on lifestyle-based strategies that support healthy aging and may help delay physical frailty in older adults.