The gut-heart axis in cardio-oncology

As cancer survival rates improve, the long-term burden of treatment has become increasingly evident. Cancer survivors face a markedly higher risk of cardiovascular-related complications and premature, non-cancer-related mortality. In particular, cardiovascular disease (CVD) is disproportionately prevalent, with survivors approximately 40% more likely to develop and die from CVD compared to the general population. Although this increased morbidity reflects both acute cardiotoxic events and the later development and progression of more chronic CVDs, traditionally viewed as direct consequences of cancer therapies, the underlying mechanisms, especially those that are feasible to modify, are poorly understood. Emerging evidence positions the gut-heart axis as a central regulator of cardiovascular risk in cardio-oncology. This avenue is especially compelling to explore as the gut microbiome is well documented to be altered by cancer therapies, including chemotherapy, immune checkpoint inhibitors, targeted therapies, and radiation, with profound and persistent changes in diversity, composition and function widely reported across clinical cohorts. Comparable microbial changes have been observed in non-cancer cohorts with cardiovascular disease. For example, specific microbial metabolites have been reported to exert cardiovascular protective benefits in hypertension. Thus, there is a compelling opportunity to explore the gut microbiome to advance our understanding and ability to prevent cardiovascular disease in cancer survivors. This review synthesizes current evidence linking the gut microbiome to cancer therapy-related cardiac dysfunction (CTRCD), evaluates microbial metabolites as predictive biomarkers of cardiotoxicity, and discusses microbiome-targeted modulation as an emerging strategy for improving cardiovascular outcomes in cancer survivors.