The Gut–Kidney–Heart Axis: Unraveling the Molecular Mechanisms and Emerging Perspectives in Cardiorenal Syndrome: A Narrative Review

Cardiorenal syndrome (CRS) represents a complex interplay between cardiac and renal dysfunction, increasingly recognized as part of a broader multiorgan network that includes the gastrointestinal tract. Emerging evidence highlights the gut–kidney–heart (GKH) axis as a central contributor to CRS pathophysiology through mechanisms involving dysbiosis, microbial metabolite overload, immune activation, endothelial injury, and neurohormonal imbalance. This narrative review synthesizes current knowledge on the molecular pathways linking the gut microbiome with cardiac and renal dysfunction, emphasizing the roles of trimethylamine N-oxide, short-chain fatty acids, uremic toxins, and inflammatory mediators. It further explores diagnostic innovations, therapeutic opportunities, and future research directions, including precision microbiome-based interventions, metabolite-targeted therapies, and AI-driven risk stratification. Understanding the biological and translational relevance of the GKH axis provides a strong foundation for developing more personalized and effective strategies in managing CRS.