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

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 microbiota, 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 microbiota 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/VisMS/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 dehydroxylated metabolites could, however, not be identified. Conclusions: trans-Resveratrol metabolism by human gut microbiota shows pronounced interindividual differences, which should be taken into account during investigation of health-related effects of this stilbene. This trial was registered at the German Clinical Trials Register as DRKS00004311, Universal Trial Number (WHO) UTN: U1111-1133-4621. Am J Clin Nutr 2013;97:295-309.