Intestinal pharmacokinetics of resveratrol and regulatory effects of resveratrol metabolites on gut barrier and gut microbiota.

Resveratrol, a dietary polyphenol, has a variety of intestinal bioactivities. However, its material basis remains unknown. This study examined the intestinal pharmacokinetics of resveratrol using HPLC-MS/MS. After oral ingestion in mice, resveratrol and its sulfation metabolites were identified in copious amount in the entire intestinal tract and feces. The glucuronidation metabolites were found in major quantity only in the small intestine. The amount of resveratrol and its metabolites in the total intestine peaked at 4 h, with a concentration of 200 ± 74.8 μM, which corresponded to 14.0% of the administrated dose. During in vitro fermentation, resveratrol-3-O-sulfate, but not resveratrol, significantly promoted the growth of Lactobacillus reuteri (10-fold higher). During the incubation with Caco-2 cells, resveratrol-3-O-sulfate significantly up-regulated the mRNA expressions of tight junction and mucin-related proteins. In conclusion, the intestinal concentration of resveratrol could partially support its intestinal bioactivities, which may be mediated through the actions of its metabolites.