Application of a dynamic colonic gastrointestinal digestion model to red wines: a study of flavanol metabolism by the gut microbiota and the cardioprotective activity of microbial metabolites†

Over the last decade, research has emphasized the role of the microbiome in regulating cardiovascular physiology and disease progression. Understanding the interplay between wine polyphenols, the gut microbiota, and cardiovascular health could provide valuable insights for uncovering novel therapeutic strategies aimed at preventing and managing cardiovascular disease. In this study, two commercial red wines were subjected to in vitro dynamic gastrointestinal digestion (GIS) to monitor the flavanol–microbiota interaction by evaluating the resulting microbial metabolites. Furthermore, the cardiovascular protective activity of wine flavanol microbial metabolites was investigated, integrating their effects on antihypertensive activity, cholesterol metabolism and insulin resistance into human endothelial (EA.hy926) and hepatic (HepG2) cell lines. A significant production of microbial flavanol metabolites, with a prevalence of phenylpropionic and phenylacetic acids, valerolactones and short chain fatty acids such as butyric acid, was observed, particularly in the transverse and descending colon sections. Incubating HAECs and HepG2 cells with the colon improved cardioprotective parameters. Specifically, an increase in the vasodilator NO, an improvement in the LDL receptors and the HMGCoA enzyme, with positive effects on cholesterol metabolism, and the reduction of glycogen levels improving insulin resistance were observed.