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

TL;DR

This study finds that elevated TMAO levels in the blood are linked to heart failure with reduced ejection fraction and could serve as a useful biomarker.

Contribution

The study demonstrates TMAO's independent association with HFrEF severity and its potential as a biomarker when combined with clinical data.

Findings

TMAO levels were significantly higher in HFrEF patients compared to healthy controls.

TMAO correlated with impaired cardiac function and lower serum albumin in HFrEF patients.

Combining TMAO with clinical covariates improved HFrEF discrimination (AUC = 0.967).

Abstract

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]) (p < 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, p = 0.036; OR 2.05, 95% CI 1.18–3.57, p = 0.010, respectively) and albumin (OR 0.56, 95% CI 0.36–0.89, p = 0.015; OR 0.61, 95% CI 0.39–0.93, p = 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.

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