Gut Failure: A Review of the Pathophysiology and Therapeutic Potentials in the Gut-Heart Axis

Despite considerable advances, heart failure (HF) continues to cause high morbidity and mortality. Chronic low-grade inflammation is a hallmark of HF, but the exact mechanisms remain incompletely defined. The gut is a potential source of systemic inflammation through dysbiosis, an imbalance of beneficial and harmful metabolites, disruption of intestinal barrier integrity, and bacterial translocation. Conversely, HF-related congestion and hypoperfusion adversely affect gut structure and function, creating a vicious cycle. Short-chain fatty acids (SCFAs) appear protective, whereas trimethylamine-N-oxide (TMAO) and some amino acid–derived metabolites (e.g., indoxyl sulfate; kynurenine pathway products) are linked to adverse cardiovascular outcomes. Based on these insights, multiple therapeutic strategies—dietary patterns, microbial enzyme inhibition, hepatic FMO3 inhibition, pre/probiotics, antibiotics, and anti-inflammatory agents—are being explored to modulate the gut-heart axis. This review summarizes gut-related causative pathways implicated in HF pathophysiology and the associated therapeutic interventions described in the literature.