Abstract
As the "second genome" of the human body, the intestinal microbiota plays a key role in preventing the onset and progression of obesity, metabolic disorders, and inflammatory diseases by modulating immune function, maintaining metabolic homeostasis, and reinforcing mucosal barrier integrity. This review systematically investigates the biological and physiological mechanisms underlying the interaction between exercise and the gut microbiota in disease prevention. Existing evidence suggests that exercise, as a non-pharmacological intervention, can prevent and manage obesity, diabetes, and neurodegenerative diseases by reshaping the composition and function of the gut microbiota, suppressing oxidative stress, reducing inflammatory markers, and maintaining intestinal mucosal barrier homeostasis. Current evidence has begun to elucidate the molecular mechanisms by which the gut microbiota mediates disease prevention and progression under varying exercise intensities, modalities, and durations. However, the structural and functional changes of the gut microbiota induced by different exercise doses remain insufficiently characterized, limiting the ability to establish clear exercise-dose relationships for disease prevention. This article systematically reviews the fundamental characteristics of the gut microbiota and the physiological mechanisms underlying exercise intervention in disease prevention through the microbiota, with a focus on exploring the interaction network among the microbiota, exercise, and disease states. Although exercise-induced regulation of the gut microbiota and its metabolites, including short-chain fatty acids (SCFAs), tryptophan metabolites, and bile acids, has demonstrated adaptive and regulatory advantages in disease prevention, the specific effects of exercise-driven changes in the microbiota on various diseases still require extensive experimental validation. In the future, greater attention should be given to the differential effects of varying exercise doses on individual gut microbiota profiles, as well as the long-term impact of exercise-modulated gut microbiota on disease outcomes. On this basis, novel therapeutic strategies should be proposed to promote the enrichment of exercise-responsive microbial populations and harness the protective potential of the gut microbiota for disease prevention.