In recent years, gut microbiota has emerged as a central modulator of cardiovascular health and disease. This has led to a transition from the old understanding of cardiovascular pathology as a largely cardiac-centric problem to a systemic, multi-organ process. A growing body of evidence demonstrates that changes in the makeup of gut microbes, generally called dysbiosis, are significant in the development and progression of cardiovascular illnesses, including heart failure. Moreover, there are bidirectional interactions between the failing heart and the gut. In heart failure, impaired hemodynamics and venous congestion further worsen intestinal hypoperfusion and barrier dysfunction in a self-perpetuating cycle that exacerbates dysbiosis and systemic inflammation. The gut–heart axis offers a fresh paradigm for illness progression beyond classical neurohormonal and hemodynamic processes. The gut microbiota acts as an endocrine organ by producing bioactive metabolites such as TMAO (trimethylamine N-oxide), SCFA (short-chain fatty acids) and bile acids, which, via several routes, have a serious impact on host health and disease. This narrative review aims to summarize the current evidence for the gut microbiota as a new cardiovascular risk factor, focusing on biological mechanisms and clinical and epidemiological evidence.

Background/Objectives: Advanced heart failure (HF) carries a high symptom burden and mortality, and identifying the right time for palliative and advanced-therapy discussions remains difficult. We systematically reviewed the prognostic value of serological biomarkers, echocardiographic indices, and patient-reported outcomes (PROs) in advanced HF. Methods: PubMed, Scopus, Web of Science, and the Cochrane Library were searched on 1 June 2026 for studies published within the prior 10 years, following PRISMA 2020 (PROSPERO CRD420261505929). Risk of bias was assessed with the Newcastle–Ottawa Scale and certainty of evidence with GRADE. Hazard ratios (HRs) for all-cause mortality were pooled with random-effects models within pathophysiologically defined serological subgroups; markers with opposing prognostic directions were synthesized narratively. Results: Of 3866 records, 37 studies (approximately 31,849 patients) were included; 29 (78%) were at low risk of bias. The pooled HR was 1.35 (95% CI 1.06–1.74; k = 4; I² = 92%) for neurohormonal/congestive markers; exploratory two-study estimates were 1.75 (1.50–2.04; I² = 6%) for renal/cardiorenal and 2.17 (0.85–5.52; I² = 86%) for inflammatory-nutritional markers. GRADE certainty was Low for the renal/cardiorenal estimate and Very Low for the other two, and funnel-plot asymmetry suggested small-study effects. Echocardiographic and PRO markers were individually associated with prognosis but showed opposing directions within outcome categories and were not pooled. Conclusions: Serological, echocardiographic, and patient-reported markers each carry prognostic information in advanced HF, but the pooled estimates are exploratory. Most studies assessed mortality or hospitalization rather than palliative or advanced-therapy decisions; relevance to such decisions is interpretive and requires prospective confirmation.

The gut microbiota is increasingly recognized as an important modulator of cardiovascular health, demonstrating complicated interactions among diet, metabolism, immunology and host physiology. Evidence is accumulating that changes in the composition and function of the gut microbiome may contribute to the pathogenesis of atherosclerosis, hypertension, heart failure, thrombosis and other cardiovascular phenotypes through mechanisms involving microbial metabolites, intestinal barrier dysfunction, inflammation and metabolic dysregulation. In this context, the key question of this narrative review is: how far can modulation of the gut microbiome and its metabolic functions be a clinically meaningful approach in the prevention and treatment of cardiovascular disease, and which of the currently available microbiome-targeted approaches have sufficient mechanistic and clinical evidence to justify translation into cardiovascular practice? To answer this question, we review the evidence linking the gut microbiome to major cardiovascular phenotypes, such as atherosclerosis, hypertension, heart failure, thrombosis and atrial fibrillation, with particular focus on the mechanisms through which microbial metabolites, intestinal barrier dysfunction, inflammation and metabolic dysregulation may affect cardiovascular risk. We then review current and emerging strategies for microbiome modulation, including dietary interventions, prebiotics, probiotics, synbiotics, postbiotics, fecal microbiota transplantation and targeted inhibition of microbial metabolic pathways such as trimethylamine (TMA)/trimethylamine N-oxide (TMAO) production. We also examine bidirectional interactions between cardiovascular drugs and gut microbiome and the role of these interactions in the development of precision methods to cardiovascular prevention and treatment. Finally, we outline the major limitations of the current evidence and highlight goals for future mechanistic, translational and clinical research.