Gut-derived short-chain fatty acids bridge cardiac and systemic metabolism and immunity in heart failure

Heart failure (HF) represents a group of complex clinical syndromes with high morbidity and mortality and has a significant global health burden. Inflammation and metabolic disorders are closely related to the development of HF, which are complex and depend on the severity and type of HF and common metabolic comorbidities such as obesity and diabetes. An increasing body of evidence indicates the importance of short-chain fatty acids (SCFAs) in regulating cardiac function. In addition, SCFAs represent a unique class of metabolites and play a distinct role in shaping systemic immunity and metabolism. In this review, we reveal the role of SCFAs as a link between metabolism and immunity, which regulate cardiac and systemic immune and metabolic systems by acting as energy substrates, inhibiting the expression of histone deacetylase (HDAC) regulated genes and activating G protein-coupled receptors (GPCRs) signaling. Ultimately cardiac efficiency is improved, cardiac inflammation alleviated and cardiac function in failing hearts enhanced. In conclusion, SCFAs represent a new therapeutic approach for HF.