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TMAO: how gut microbiota contributes to heart failure

March 18, 2025

  • Cardiovascular Health
    Cardiovascular Health

    Recent research has revealed that specific gut microbiota-derived metabolites are strongly linked to cardiovascular disease risk—potentially influencing atherosclerosis development more than traditional risk factors like cholesterol levels. This highlights the gut microbiome as a novel therapeutic target for cardiovascular interventions.

Last Updated: 2024

Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.

Karen Pendergrass

Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.

What Was Reviewed?

This review focused on the involvement of gut microbiota in the pathogenesis and progression of cardiovascular diseases, particularly heart failure (HF). It emphasized the role of gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) in heart failure and explored the potential of the gut–TMAO–HF axis as a therapeutic target for HF treatment.

Who Was Reviewed?

The review considered patients with various forms of heart failure, including acute heart failure (AHF), chronic heart failure (CHF), heart failure with preserved ejection fraction (HFpEF), and heart failure with reduced ejection fraction (HFrEF). It also encompassed studies involving animal models and in vitro experiments that investigated the pathophysiological mechanisms of TMAO in HF.

What Were the Most Important Findings of This Review?

This review highlights the critical role of gut microbiota in heart failure (HF). Gut dysbiosis contributes to HF pathogenesis through mechanisms like splanchnic hypoperfusion and intestinal barrier dysfunction. Trimethylamine N-oxide (TMAO), a gut-derived metabolite, significantly impacts cardiovascular pathology by promoting myocardial hypertrophy and fibrosis, inducing inflammatory responses, and causing endothelial dysfunction. Elevated TMAO levels correlate with poorer prognosis and higher mortality in HF patients, serving as an independent predictor for HF outcomes. Potential therapeutic targets include dietary interventions, probiotics, prebiotics, and inhibitors of TMA synthesis, such as 3,3-dimethyl-1-butanol (DMB). Fecal microbial transplantation (FMT) and certain antibiotics also show promise in modulating gut microbiota and reducing TMAO production. These findings support a multifaceted approach to HF management by targeting gut microbiota and its metabolites.

What Are the Greatest Implications of This Review?

The “TMAO: how gut microbiota contributes to heart failure” review highlights the importance of novel therapeutic strategies, the prognostic value of TMAO, and future research directions.

Novel Therapeutic Strategies: The review suggests that targeting the gut–TMAO–HF axis could be a revolutionary approach in treating HF. By modulating gut microbiota composition and reducing TMAO levels, it may be possible to improve HF prognosis and patient outcomes. Personalized dietary interventions and the use of probiotics, prebiotics, and phytochemicals hold significant potential for HF management.

Prognostic Value of TMAO: TMAO can serve as a valuable prognostic marker for HF, aiding clinicians in identifying high-risk patients and tailoring more effective treatment strategies. Further research is needed to validate TMAO’s role across diverse populations and to explore its utility in clinical practice.

Future Research Directions: Prospective studies are needed to establish a causal relationship between gut microbiota changes and HF. Investigating the detailed mechanisms of how TMAO influences HF progression will be crucial for developing targeted therapies.

Heart Failure

Recent research reveals that the gut microbiome significantly influences heart failure progression, contributing to inflammation and other complications.

Trimethylamine N-Oxide (TMAO)

TMAO is a metabolite formed when gut bacteria convert dietary nutrients like choline and L-carnitine into trimethylamine (TMA), which is then oxidized in the liver to TMAO. This compound is linked to cardiovascular disease, as it promotes atherosclerosis, thrombosis, and inflammation, highlighting the crucial role of gut microbiota in influencing heart health.

Trimethylamine N-Oxide (TMAO)

TMAO is a metabolite formed when gut bacteria convert dietary nutrients like choline and L-carnitine into trimethylamine (TMA), which is then oxidized in the liver to TMAO. This compound is linked to cardiovascular disease, as it promotes atherosclerosis, thrombosis, and inflammation, highlighting the crucial role of gut microbiota in influencing heart health.

Fecal Microbiota Transplantation (FMT)

Fecal Microbiota Transplantation (FMT) involves transferring fecal bacteria from a healthy donor to a patient to restore microbiome balance.

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