Modulation of the gut-heart axis by exercise in diabetic cardiomyopathy: Microbial mechanisms and clinical implications

Diabetic cardiomyopathy (DCM) is a common complication of diabetes, a leading cause of diabetes-related mortality. Growing evidence indicates a strong association between gut microbiota dysbiosis and the development and progression of DCM. This dysbiosis disrupts intestinal barrier integrity and alters metabolite profiles, including short-chain fatty acids, bile acids, trimethylamine-N-oxide, lipopolysaccharide, branched-chain amino acids, hydrogen sulfide, and tryptophan metabolites, thereby promoting inflammation, oxidative stress, and metabolic dysfunction through the gut-heart axis, ultimately contributing to the pathogenesis of DCM. Studies have shown that exercise reshapes gut microbiota composition, enhances intestinal barrier function, and modulates the production of microbial metabolites in individuals with diabetes. Exercise has been recommended as a first-line intervention for patients with DCM. However, whether exercise prevents and treats DCM through gut microbiota regulation and the underlying mechanisms of this interaction remain largely unclear. This review summarizes current evidence linking exercise, gut microbiota, and DCM, emphasizing the potential role of gut microbiota in mediating the cardioprotective effects of exercise in diabetes. Understanding how exercise modulates the gut-heart axis may open new avenues for microbiota-based strategies to prevent and manage DCM.