Exercise-Associated Gut Microbiota Remodeling and Cardiovascular Protection: Potential Mechanisms Involving Inflammatory Regulation

Cardiovascular disease (CVD) remains a major contributor to global mortality and disease burden and encompasses a range of conditions commonly associated with metabolic disturbances, endothelial dysfunction, and chronic inflammation. Emerging evidence suggests that persistent low-grade inflammation contributes to the development and progression of CVD and represents an important component of its pathophysiology. The gut microbiota (GM) and microbiota-related metabolites are increasingly recognized as important regulators of host metabolism and immune homeostasis. GM dysbiosis may influence cardiovascular inflammation through alterations in microbial metabolites, intestinal barrier function, and inflammatory signaling, including the TLR4/NF-κB/NLRP3 pathway and immunoregulatory mechanisms involving IL-10 and context-dependent TGF-β signaling. Accumulating experimental and clinical evidence suggests that exercise may reshape GM composition and microbial metabolic profiles and may be associated with changes in inflammatory and immunoregulatory responses relevant to cardiovascular health. Evidence from atherosclerosis, hypertension, myocardial infarction, and myocardial ischemia–reperfusion injury further supports disease-specific associations among exercise, GM alterations, inflammatory signaling, and cardiovascular outcomes. Therefore, this review synthesizes current mechanistic, animal, and human evidence on these interconnected processes, with particular emphasis on the TLR4/NF-κB/NLRP3 and IL-10/TGF-β-related signaling pathways. Overall, current evidence supports disease-specific associations and potential mechanistic links among exercise, GM alterations, microbial metabolites, inflammatory regulation, and cardiovascular outcomes; however, the GM has not yet been established as a universal or causal mediator of exercise-related cardiovascular protection.