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 -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.

Resveratrol modulates the gut microbiota to prevent murine colitis development through induction of Tregs and suppression of Th17 cells

“…More recent studies have shown that resveratrol may protect against many clinical disorders by modulating the gut microbiota . However, such studies did not perform fecal transfer experiments to demonstrate that the microbiota altered by resveratrol treatment could lead to suppression of colitis‐associated inflammation.…”

“…37 More recent studies have shown that resveratrol may protect against many clinical disorders by modulating the gut microbiota. [41][42][43] However, such studies did not perform fecal transfer experiments to demonstrate that the microbiota altered by resveratrol treatment could lead to suppression of colitis-associated inflammation. In the present report, we therefore performed fecal transfer experiments, which conclusively demonstrated that resveratrol-mediated modulations in the gut microbiota are indeed responsible for attenuating colonic inflammation.…”

Endothelial Cells Deconjugate Resveratrol Metabolites to Free Resveratrol: A Possible Role in Tissue Factor Modulation

“…On the other hand, piceid is deglycosylated to RV by a glycosidase enzyme before being absorbed in the intestine and undergoing phase‐II metabolism to generate RVmet . The concentrations of these RVmet forms far exceeds the concentrations of their parent compound (free RV) in serum . This evidence has prompted doubts about the clinical impact of the benefits of the native structure of RV observed in preclinical studies.…”

The Regulation of Host Intestinal Microbiota by Polyphenols in the Development and Prevention of Chronic Kidney Disease

“…Resveratrol is an antifungal and antibacterial stilbenoid derived from plants and can be obtained from diets consisting of various fruits such as grapes and their juice, oranges and cranberries, red currants and peanut skins (33). In both in vitro and in vivo studies, resveratrol has proved to be an effective antioxidant, antibacterial, anti-obesity, anti-inflammatory, and anti-cancer agent (34)(35)(36).…”

“…In addition, resveratrol has been shown to facilitate the assembly of close junction protein claudine 4, which may reverse the increase in intestinal permeability caused by the widespread mycotoxin deoxynivaenol. Given the role of resveratrol in maintaining an intact intestinal barrier and the "leaky gut" pathophysiology present in several mechanisms of disease, this research avenue warrants further investigation (33).…”