Gut Microbiota: A Novel Regulator of Cardiovascular Disease and Key Factor in the Therapeutic Effects of Flavonoids

Abstract

Cardiovascular disease is the main cause of death worldwide, and traditional cardiovascular risk factors cannot fully explain the occurrence of the disease. In recent years, the relationship between gut microbiota and its metabolites and cardiovascular disease has been a hot study topic. The changes in gut microbiota and its metabolites are related to the occurrence and development of atherosclerosis, myocardial infarction, heart failure, and hypertension. The mechanisms by which gut microbiota and its metabolites influence cardiovascular disease have been reported, although not comprehensively. Additionally, following ingestion, flavonoids are decomposed into phenolic acids that are more easily absorbed by the body after being processed by enzymes produced by intestinal microorganisms, which increases flavonoid bioavailability and activity, consequently affecting the onset of cardiovascular disease. However, flavonoids can also inhibit the growth of harmful microorganisms, promote the proliferation of beneficial microorganisms, and maintain the balance of gut microbiota. Hence, it is important to study the relationship between gut microbiota and flavonoids to elucidate the protective effects of flavonoids in cardiovascular diseases. This article will review the role and mechanism of gut microbiota and its metabolites in the occurrence and development of atherosclerosis, myocardial infarction, heart failure, and hypertension. It also discusses the potential value of flavonoids in the prevention and treatment of cardiovascular disease following their transformation through gut microbiota metabolism.

Keywords: cardiovascular disease; flavonoid; gut microbiota; interactions; metabolite.

FIGURE 1

The role of gut microbiota in cardiovascular disease and flavonoid metabolism. The GM produces TMA by ingesting choline (such as choline, phosphatidylcholine and l–carnitine) from food. TMA enters the liver through the hepatointestinal circulation, and forms TMAO through the oxidation of flavin monooxygenase, then enters the systemic circulation. Circulating TMAO levels increase, causing foam cells and platelets to accumulate, while affecting cholesterol transport, thereby promoting atheromatous plaque formation.

FIGURE 2

Effects of gut microbiota and its metabolites on atherosclerosis, myocardial infarction, heart failure and hypertension. The interaction between diet and gut microbiota may promote the development of cardiovascular disease through common and different mechanisms. Western food rich in red meat promotes the production of TMA by bacteria, which is oxidized to TMAO in liver. TMAO may participate in atherosclerosis by interfering with cholesterol transport, foam cell formation and platelet aggregation. The effect of TMAO on blood pressure was mainly manifested in its enhancement of pressure-raizing effect of Ang II. Platelet aggregation also plays a role in atherosclerosis. The decrease of dietary fiber is related to the decrease of bacterial production of SCFAs, which play an immunomodulatory role in intestinal mucosa. The decrease of SCFAs level can promote local inflammation, aggravate intestinal ecological imbalance, and lead to the damage of intestinal barrier function. The damage of intestinal barrier function leads to the leakage of bacterial toxins, which further aggravates local and systemic inflammation. In addition, dysbiosis destroys the intestinal mucosal barrier, leading to gut microbiota entering the systemic circulation, which increases the incidence of adverse cardiovascular events after MI and aggravates the progress of HF. The roles of gut microbiota and its metabolites in hypertension.