The gut–heart axis in sepsis-induced cardiomyopathy: pathophysiology, microbial metabolites, and cardiovascular insights

Sepsis-induced cardiomyopathy (SICM) is a frequent yet potentially reversible form of acute myocardial dysfunction associated with high morbidity and mortality in septic shock. Increasing evidence suggests that alterations in the gut microbiota contribute to systemic inflammation and metabolic dysregulation during sepsis, highlighting the emerging importance of the gut–heart axis. However, the specific mechanisms through which microbiome-derived signals influence acute cardiac dysfunction remain incompletely understood. In this review, current evidence on gut microbial dysbiosis, metabolite-mediated signaling, and myocardial pathophysiology was synthesized to propose an integrative conceptual framework in which SICM represents a form of acute cardio-metabolic failure driven by time-dependent gut-derived inflammatory and metabolic perturbations. Key microbial metabolites, including short-chain fatty acids, bile acids, indole derivatives, trimethylamine-N-oxide, and phenylacetylglutamine, exert context-dependent effects on immune activation, mitochondrial energetics, calcium handling, and microcirculatory function. Notably, emerging data highlight important mechanistic paradoxes, such as divergent roles of specific metabolites in chronic cardiovascular disease versus acute sepsis, underscoring the need for disease/stage-specific interpretation of microbiome signaling. Translational challenges and opportunities for microbiome-targeted interventions in SICM were further discussed, including patient phenotyping, therapeutic timing, and integration with cardiac-focused supportive strategies in the intensive care setting. By positioning SICM within the broader paradigm of the gut–heart axis, this review provides a mechanistically grounded and clinically oriented perspective aimed at informing precision therapeutic approaches and future trial design in septic myocardial dysfunction.