In vivo and in vitro metabolism of trans-resveratrol by human gut microbiota

Abstract

Background: Strong interindividual differences in the microbial conversion of some dietary polyphenols have been reported. In-depth studies of trans-resveratrol metabolism by human gut micro-biota, however, are lacking, and only one bacterial metabolite, namely dihydroresveratrol, has been described. Objective: The aim of this study was to elucidate interindividual differences in trans-resveratrol metabolism by human gut micro-biota and to identify bacterial strains involved. Design: In the first part of the study, in vitro fermentation experiments were performed with feces samples from 7 healthy volunteers, and metabolite formation was measured by liquid chromatography-ultraviolet/visible (UV/Vis)-mass spectrometry (MS)/MS detection. Microbial diversities in 3 feces samples were analyzed by high-throughput pyrosequencing and quantitative real-time polymerase chain reaction. In addition, trans-resveratrol conversion experiments were conducted with selected fecal bacterial strains in pure culture. The second part of the study was a controlled intervention study with 12 healthy volunteers. After a washout period, all of the subjects received a one-time oral dose of 0.5 mg trans-resveratrol/kg body weight in the form of a grapevine-shoot supplement, and 24-h urine samples were analyzed by liquid chromatography-UV/Vis-MS/MS. Results: Besides dihydroresveratrol, 2 previously unknown bacterial trans-resveratrol metabolites were identified in vitro and in vivo: 3,4′-dihydroxy-trans-stilbene and 3,4′-dihydroxybibenzyl (lunularin). Their formation, however, varied among the volunteers. Two strains, Slackia equolifaciens and Adlercreutzia equolifaciens, were identified as dihydroresveratrol producers. Gut bacteria able to produce dehy-droxylated metabolites could, however, not be identified. Conclusions: trans-Resveratrol metabolism by human gut microbio-ta shows pronounced interindividual differences, which should be taken into account during investigation of health-related effects of this stilbene. © 2013 American Society for Nutrition.