Gut-brain-heart axis in congenital heart disease: emerging roles of the microbiome in cardiac physiology and neurodevelopment.

Abstract

Congenital heart disease (CHD) is increasingly recognised as a multisystem condition extending beyond structural cardiac abnormalities to include gastrointestinal, immunological and neurodevelopmental consequences. Although advances in surgical and intensive care have significantly improved survival, children with CHD remain at heightened risk for adverse neurodevelopmental outcomes, systemic inflammation and gastrointestinal morbidity. The gut microbiome plays a central role in immune regulation, metabolic homeostasis and brain development particularly during early life. Perturbations of the microbiome are common in infants with CHD due to altered gut perfusion, antibiotic exposure, feeding disruption and cardiopulmonary bypass (CPB). These changes may influence both cardiac recovery and neurodevelopment through interconnected gut-heart-brain signalling pathways. This review synthesises current evidence linking the gut microbiome to cardiac physiology and brain development in children with CHD, with particular emphasis on early-life vulnerability, perioperative factors and emerging translational insights. Understanding these interactions may inform future strategies to optimise long-term outcomes in this high-risk population.