TMAO: how gut microbiota contributes to heart failure

Abstract

An increasing amount of evidence reveals that the gut microbiota is involved in the pathogenesis and progression of various cardiovascular diseases. In patients with heart failure (HF), splanchnic hypoperfusion causes ischemia and intestinal edema, allowing bacterial translocation and bacterial metabolites to enter the blood circulation via an impaired intestinal barrier. This results in local and systemic inflammatory responses. Gut microbe-derived metabolites are implicated in the pathology of multiple diseases, including HF. These landmark findings suggest that gut microbiota influences the host's metabolic health, either directly or indirectly by producing several metabolites. In this review, we mainly discuss a newly identified gut microbiota-dependent metabolite, trimethylamine N-oxide (TMAO), which appears to participate in the pathologic processes of HF and can serve as an early warning marker to identify individuals who are at the risk of disease progression. We also discuss the potential of the gutÀTMAOÀHF axis as a new target for HF treatment and highlight the current controversies and potentially new and exciting directions for future research.

Trimethylamine N‐oxide and outcomes in patients hospitalized with acute heart failure and preserved ejection fraction

“…Whether high TMAO levels are a cause or result of poor prognosis of HF is controversial, 9 but, in the present study, we confirmed that high TMAO was associated with poor prognosis independent of established prognostic indicators such as previous hospitalization for HF, renal dysfunction, and anaemia. In addition, even if B‐type natriuretic peptide and nutritional indicators, BMI and GNRI, were included in the propensity score, high TMAO still remained to be associated with poor prognosis ( P < 0.05) (data not shown).…”

“…This promotes atherosclerosis and is associated with increased morbidity and mortality in coronary artery disease 10,12,13 . TMAO also directly affects the heart by inducing myocardial hypertrophy and fibrosis, 14 inflammation, 15 and mitochondrial dysfunction of the myocardium, 16 which may affect development and prognosis of HF 9 . The association between TMAO and prognosis has been investigated in patients with HF with reduced ejection fraction (HFrEF) 6,8 .…”

Nutritional Viewpoints on Eggs and Cholesterol

“…TMAO is then transported to tissues or excreted into the urine. TMAO acts atherogenic [120][121][122][123][124]. Updated systematic review and meta-analysis indicate that TMAO increased the hazard ratio (HR) of CHD mortality [125].…”

Trimethylamine N-Oxide, a Gut Microbiota-Derived Metabolite, Is Associated with Cardiovascular Risk in Psoriasis: A Cross-Sectional Pilot Study

“…Moreover, gut dysbiosis has also been linked to psoriasis and its comorbidities [33]. One of the current hypotheses for the pathophysiological mechanism linking alteration in gut microbiome with increased cardiovascular risk states that the bacterial metabolites are translocated via impaired gut barrier into the circulation and exert systemic effects [14]. Several studies confirmed intestinal barrier damage in psoriasis [16][17][18] as well as increased blood concentration of bacterial components (lipopolysaccharide, DNA) in psoriatic patients [34,35].…”

“…Plasma TMAO is a metabolite derived from dietary precursors (choline, phosphatidylcholine, and L-carnitine), through the activity of gut microbiota [10]. Several studies have revealed a relation between plasma TMAO concentration and cardiovascular diseases, such as myocardial infarction, chronic heart failure, atrial fibrillation, or stroke [11][12][13][14]. Fecal microbial transplantation in a murine model demonstrated the role of intestinal microbiota in transmission of atherosclerosis susceptibility and overall TMAO production [15].…”