Role of Gut Microbiome-derived Trimethylamine N-oxide and Short-chain Fatty Acids in Heart Failure Outcomes: A Narrative Review.

INTRODUCTION: HF continues to be a serious medical problem all over the world, resulting in significant morbidity and mortality despite advancements in therapeutic strategies. Current research indicates the involvement of the gut-heart axis in HF. Gut microbiome metabolites, including TMAO and SCFAs, affect heart structure, function, and outcomes. METHODS: We conducted a review of experimental, observational, and clinical studies to evaluate alterations in gut microbiota and metabolome in patients with HF. The literature was analyzed to study mechanisms of observed alterations, clinical associations, their potential role as biomarkers, and therapeutic strategies associated with TMAO and SCFAs. RESULTS: Higher TMAO levels generated by gut microbes from choline- and L-carnitinecontaining foods contributed to increased mortality, inflammation, and myocardial injury in HF. Conversely, SCFAs, such as acetate, propionate, and butyrate, produced during bacterial fermentation of dietary fibers promoted cardioprotection by maintaining gut integrity, enhancing immune and metabolic pathways, and promoting energy utilization in HF. In HF, the gut microbiome showed lower species diversity, reduced abundance of beneficial organisms responsible for SCFA production, and enrichment of microorganisms capable of producing TMAO. Diet played an essential role, with increased intake of dietary fiber leading to enhanced SCFAs levels and a high choline and fat content causing elevated TMAO levels. DISCUSSION: Our analysis demonstrates that gut microbiome-derived metabolites exert both harmful and beneficial effects in HF. Gut-based dietary and microbiome modulation therapy might prove useful, although well-designed prospective clinical trials are needed to confirm its efficacy. CONCLUSION: Gut microbiome-derived metabolites, particularly TMAO and SCFAs, are promising mechanistic and prognostic markers in HF. However, routine clinical measurement and microbiome- targeted therapy require prospective validation, standardized assays, and interventional trials before implementation in HF care.