Cardiovascular and Antiobesity Effects of Resveratrol Mediated through the Gut Microbiota

Abstract

Encouraging scientific research into the health effects of dietary bioactive resveratrol has been confounded by its rapid first-pass metabolism, which leads to low in vivo bioavailability. Preliminary studies have shown that resveratrol can modulate gut microbiota composition, undergo biotransformation to active metabolites via the intestinal microbiota, or affect gut barrier function. In rodents, resveratrol can modify the relative Bacteroidetes:Firmicutes ratio and reverse the gut microbial dysbiosis caused by a high-fat diet. By upregulating the expression of genes involved in maintaining tight junctions between intestinal cells, resveratrol contributes to gut barrier integrity. The composition of the gut microbiome and rapid metabolism of resveratrol determines the production of resveratrol metabolites, which are found at greater concentrations in humans after ingestion than their parent molecule and can have similar biological effects. Resveratrol may affect cardiovascular risk factors such as elevated blood cholesterol or trimethylamine N-oxide concentrations. Modulating the composition of the gut microbiota by resveratrol may affect central energy metabolism and modify concentrations of satiety hormones to produce antiobesity effects. Encouraging research from animal models could be tested in humans.

Keywords: cardiovascular disease; gut barrier integrity; inflammation; microbiome; obesity; resveratrol.

FIGURE 1

The metabolism and disposition of RES. RES is mainly absorbed in the small intestine after oral intake. It is then quickly and extensively metabolized to RES-GLU and RES-SUL forms in the intestine and the liver. The RES-GLU and RES-SUL forms are excreted by the kidney in the urine. In the human body, sulfatases and glucuronidases can convert the conjugated forms of RES back to the free RES form. Enterohepatic recycling also occurs by biliary excretion and intestinal reabsorption. Moreover, in the intestine, unabsorbed RES is converted to microbial metabolites—for example, DHR—which can also be further metabolized to DHR-GLU and DHR-SUL derivatives. Finally, the unabsorbed RES and its metabolites are excreted in the feces. DHR, dihydroresveratrol; GLU, glucuronide; RES, resveratrol; SUL, sulfate.