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From Gut to Heart: Targeting Trimethylamine N-Oxide as a Novel Strategy in Heart Failure Management

Zehui Ding, Yunfeng Yu, Jiaming Wei, Z. Wang, Ruifang Lin, Ya Li, Zhihua Guo

2025Biomolecules6 citationsDOIOpen Access PDF

Abstract

Heart failure (HF) marks the culmination of numerous cardiac pathologies, presenting a major medical hurdle in prevention and treatment. In recent years, with the advancements in genomics and metabolomics, research has demonstrated that gut microbiota plays a significant role in the pathogenesis of HF. Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite and primarily sourced from foods abundant in choline, L-carnitine, and betaine. Research has shown that patients with HF exhibit higher levels of TMAO. Accumulating evidence has indicated that TMAO directly or indirectly mediates the occurrence and development of HF through multiple mechanisms. Furthermore, TMAO functions as a crucial prognostic marker in HF. Therefore, TMAO emerges as a potential therapeutic target for HF. This article reviews the generation and metabolic pathways of TMAO, emphasizes its pathophysiological mechanisms in HF, and explores promising therapeutic approaches targeting TMAO, offering novel insights and strategies for HF management.

Topics & Concepts

Heart failureMedicineMetaboliteGut floraPathogenesisBioinformaticsMetabolomicsTrimethylamine N-oxideComputational biologyIntensive care medicinePathophysiologyGenomicsDiseaseBiologyTrimethylaminePharmacologyDiet and metabolism studiesGut microbiota and healthHeart Failure Treatment and Management