Heart failure and trimethylamine N-oxide: time to transform a ‘gut feeling’ in a fact?

In the last few years, in the context of a growing interest in investigating novel pathways involved in heart failure (HF) pathophysiology, the association between the gastrointestinal (GI) system and HF represents an important model of attention, the so called ‘gut hypothesis’.Despite being classically identified as a ‘simple’ intestinal dysfunction, the main hypothesis is currently focused on the role of inflammation and oxidative stress as a consequence of the intestinal wall ischaemia and/or congestion induced by HF, determining a gut barrier dysfunction and resulting in an increased gut bacterial translocation.With this in mind, two main mechanisms have been proposed to link gut dysfunction and HF; (i) metabolism dependent, via gut-derived metabolites entering the systemic circulation and exerting pro-atherogenic effects and pro-inflammatory effects and (ii) metabolism independent, via bacterial components (e.g. lipopolysaccharides and endotoxins) translocating in the systemic circulation and contributing to the systemic inflammatory state with its well-known negative effects on HF.