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.

Andrew Day, Bernward Lauer, Dionysis Matsiras, Sofia Bezati, Ioannis Ventoulis, Christos Verras, John Parissis, Effie Polyzogopoulou