Interindividual Differences in Human In Vitro Intestinal Microbial Conversion of Green Tea (-)-Epigallocatechin-3-O-Gallate and Consequences for Activation of Nrf2 Mediated Gene Expression

Scope: An in vitro faecal incubation model combined with reporter gene assay based testing strategy is developed to characterize interindividual differences in the gut microbial conversion of (-)-epigallocatechin-3-O-gallate (EGCG) and its consequences for potential activation of Nrf2-mediated gene expression. Method & Results: Anaerobic human faecal incubations are performed to characterize the microbial metabolism of EGCG including interindividual variability. EGCG derived intestinal microbial metabolite patterns show substantial interindividual differences that are correlated to relative microbial abundances determined by 16S rRNA sequencing. Results obtained show the time-dependent formation of gallic acid, pyrogallol, phenylpropane-2-ols, phenyl-γ-valerolactones, and 5-(3′,5′-dihydroxyphenyl)valeric acid as the major metabolites, with substantial interindividual differences. The activity of the formed metabolites in the activation of EpRE-mediated gene expression is tested by EpRE-LUX reporter gene assay. In contrast to EGCG, at low micromolar concentrations, especially gallic acid, pyrogallol, and catechol induce significant activity in the EpRE-LUX assay. Conclusions: Given these results and taking the level of formation into account, it is concluded that especially gallic acid and pyrogallol contribute to the EpRE-mediated beneficial effects of EGCG. The interindividual differences in the formation may result in interindividual differences in the beneficial effects of EGCG and green tea consumption.