Gut Microbiota-Derived Metabolite and Heart Failure with Reduced Ejection Fraction (HFrEF): Elevated Trimethylamine N-Oxide (TMAO) as a Potential Biomarker

Gut-derived metabolites, particularly trimethylamine N-oxide (TMAO), have been implicated in the pathophysiology of heart failure (HF). This study investigated the associations between TMAO, cardiac function, and clinical parameters to evaluate TMAO's potential as a biomarker for heart failure with reduced ejection fraction (HFrEF). Forty HFrEF patients and forty-one matched healthy controls were recruited for serum TMAO quantification using enzyme-linked immunosorbent assay (ELISA). Associations were examined using Spearman correlation and regression models. TMAO levels were significantly elevated in HFrEF patients (3.64 µM [IQR 3.00-4.31]) compared with controls (1.22 µM [IQR 0.92-2.36]) (<i>p</i> < 0.05). Elevated TMAO correlated with impaired cardiac structural and functional parameters, as well as lower serum albumin. Multinomial regression revealed that both TMAO (OR 1.83, 95% CI 1.04-3.23, <i>p</i> = 0.036; OR 2.05, 95% CI 1.18-3.57, <i>p</i> = 0.010, respectively) and albumin (OR 0.56, 95% CI 0.36-0.89, <i>p</i> = 0.015; OR 0.61, 95% CI 0.39-0.93, <i>p</i> = 0.022, respectively) were independently associated with HFrEF severity, showing significant correlations in both mildly (EF 30-40%) and moderately (20-30%) reduced EF groups. Receiver operating characteristic (ROC) analyses showed that TMAO had good discriminative ability for HFrEF (AUC = 0.853), and it improved when combined with clinical covariates (AUC = 0.967), supporting its role as a potential biomarker. These findings support integrating this gut-derived metabolite and nutritional marker into HFrEF risk stratification frameworks.