The gut microbiome in coronary artery disease and heart failure: Current knowledge and future directions

Abstract

Host-microbiota interactions involving inflammatory and metabolic pathways have been linked to the pathogenesis of multiple immune-mediated diseases and metabolic conditions like diabetes and obesity. Accumulating evidence suggests that alterations in the gut microbiome could play a role in cardiovascular disease. This review focuses on recent advances in our understanding of the interplay between diet, gut microbiota and cardiovascular disease, with emphasis on heart failure and coronary artery disease. Whereas much of the literature has focused on the circulating levels of the diet- and microbiota-dependent metabolite trimethylamine-N-oxide (TMAO), several recent sequencing-based studies have demonstrated compositional and functional alterations in the gut microbiomes in both diseases. Some microbiota characteristics are consistent across several study cohorts, such as a decreased abundance of microbes with capacity for producing butyrate. However, the published gut microbiota studies generally lack essential covariates like diet and clinical data, are too small to capture the substantial variation in the gut microbiome, and lack parallel plasma samples, limiting the ability to translate the functional capacity of the gut microbiomes to actual function reflected by circulating microbiota-related metabolites. This review attempts to give directions for future studies in order to demonstrate clinical utility of the gut-heart axis.

Keywords: Atherosclerosis; Butyrate; Coronary artery disease; Diet; Fiber; Gut microbiota; Heart failure; Metabolites; Microbiome; TMAO.

Fig. 1

Diet-gut-heart interactions: proposed mechanisms. Interactions between diet and the gut microbiome could contribute to atherosclerosis, acute coronary syndromes and heart failure through common and separate mechanisms. Westernized food rich in red meat promotes bacterial production of TMA, which is oxidized in the liver to the pro-atherogenic metabolite TMAO. TMAO may contribute to atherosclerosis by interference with cholesterol transportation, foam cell formation and platelet aggregation, the latter playing a potential role in acute coronary syndromes. Reduced dietary fiber is associated with reduced bacterial production of the short chain fatty acid butyrate, which has immune modulatory effects in the gut mucosa, and also serves as the main energy substrate for colonocytes. Reduction of butyrate levels in the gut could promote local inflammation, aggravate dysbiosis and contribute to impaired gut barrier function, the latter resulting in leakage of bacterial toxins such as LPS, further fueling local and systemic inflammation. FMO3; flavin-containing monooxygenase 3, LPS; lipopolysaccharide, TMA; trimetylamine, TMAO; trimethylamine-N-oxide. Printed with permission from Kari Toverud ©.