Nowadays, more and more evidence points out to the interrelationship between intestinal microbiota and cardiovascular diseases. Gut microbiota is composed of a large number of microorganisms that live in the human gut and are involved in many physiological processes. Changes in the composition and activity of intestinal microbiota may lead or may accelerate the evolution of some cardiovascular diseases. Alterations in the composition of gut microbiota will induce dysbiosis, causing inflammation and initiating the development of cardiovascular diseases. These alterations may be secondary to intestinal infections, exposure to some environmental factors, changes in dietary habits, high stress, use of antibiotics. Studies have shown that gut microbiota is composed of six families, the Firmicutes, Bacteroidetes, Proteobacteria, Actino-bacteria, Fusobacteria, and Verrucomicrobia phyla(1). These microorganisms are involved in the immune processes of the host, the fight against the pathogenic microorganisms and also in maintaining the integrity of intestinal barriers.
Coronary heart disease and arterial hypertension are chronic diseases with a high prevalence. Some studies have demonstrated a link between the composition of gut microbiota and the increased risk of atherosclerosis, which is the main cause of coronary heart disease(2,3). These studies have identified different species of bacteria, both in the gut and in the atheromatous plaques, suggesting that gut is a source of atherogenic bacteria(2,3). The mechanisms by which these bacteria can initiate the atherosclerotic process (or in some cases protect against it) are still unknown. Trimethylamine N-oxide (TMAO) is a microbial metabolite that was studied for its effects on cardiovascular diseases after the discovery of a positive correlation between the serum level of TMAO and the atherosclerotic plaque area. This correlation was partially explained by the role that TMAO plays in the inhibition of reverse cholesterol transport and the accumulation of macrophage cholesterol(4,5). One study has found that the TMAO level in patients with an acute coronary syndrome is an independent predictor of short-term and long-term major adverse cardiac events(6). The implication of gut microbiota in arterial hypertension has been demonstrated by animal studies(7,8). Adnan et al have shown that the blood pressure can be influenced by the exchange of gut microbiota between spontaneously hypertensive rats and Wistar-Kyoto rats(7). The ratio of Firmicutes and Bacteroidetes is considered specific for intestinal dysbiosis(9). In animal studies, the alteration of this ratio correlated with arterial hypertension, suggesting that gut microbiota could be a potential target of future antihypertensive therapies(9).
Heart failure is the final stage of evolution of the majority of cardiovascular diseases, with high mortality rates. One study has comparatively analyzed the bacteria and fungi in the feces of patients with heart failure with those of healthy controls and demonstrated that patients with chronic heart failure have more pathogenic bacteria10. Moreover, some species, like Candida, Shigella, and Campylobacter, were positively correlated with the severity of the heart failure(10). Patients with heart failure, with decreased cardiac output, have gastrointestinal mucosa congestion and ischemia, with subsequent alterations in the composition of gut microflora and also intestinal functions. These alterations will lead to bacterial translocation, the release of endotoxins in the circulation, promoting a systemic inflammatory response. Some authors suggested that TMAO can be used as a biomarker for prognosis stratification in patients with heart failure(11, although the exact mechanisms of increased levels of TMAO in patients with heart failure are still unknown. Other gut microbiota metabolites, p-cresyl sulfate and phenylacetylglutamine, have been suggested by some studies to be involved in the appearance of cardiovascular diseases(12,13).
Based on the above findings, the future cardiovascular therapies may include gut microbiota and their metabolites as potential targets. These therapies could be represented not only by drugs but also by diet changes and supplementation with prebiotics and/or probiotics.
International Secretary General of the Balkan Medical Union
President of the Romanian National Section