Dataset Information

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

ABSTRACT:

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???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. The present study characterizes the gut microbial conversion of (?)?epigallocatechin?3?O?gallate (EGCG) using anaerobic incubation model. Substantial interindividual differences are found in the formation of EGCG gut microbial metabolites. In contrast to EGCG, at low micromolar concentrations, especially metabolites gallic acid, pyrogallol, and catechol induce significant activity in the activation of Nrf2?mediated gene expression.

SUBMITTER: Liu C

PROVIDER: S-EPMC7900971 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Project description:Trisomy of human chromosome 21 (Down syndrome, DS) alters development of multiple organ systems, including the face and underlying skeleton. Besides causing stigmata, these facial dysmorphologies can impair vital functions such as hearing, breathing, mastication, and health. To investigate the therapeutic potential of green tea extracts containing epigallocatechin-3-gallate (GTE-EGCG) for alleviating facial dysmorphologies associated with DS, we performed an experimental study with continued pre- and postnatal treatment with two doses of GTE-EGCG supplementation in a mouse model of DS, and an observational study of children with DS whose parents administered EGCG as a green tea supplement. We evaluated the effect of high (100 mg/kg/day) or low doses (30 mg/kg/day) of GTE-EGCG, administered from embryonic day 9 to post-natal day 29, on the facial skeletal development in the Ts65Dn mouse model. In a cross-sectional observational study, we assessed the facial shape in DS and evaluated the effects of self-medication with green tea extracts in children from 0 to 18 years old. The main outcomes are 3D quantitative morphometric measures of the face, acquired either with micro-computed tomography (animal study) or photogrammetry (human study). The lowest experimentally tested GTE-EGCG dose improved the facial skeleton morphology in a mouse model of DS. In humans, GTE-EGCG supplementation was associated with reduced facial dysmorphology in children with DS when treatment was administered during the first 3 years of life. However, higher GTE-EGCG dosing disrupted normal development and increased facial dysmorphology in both trisomic and euploid mice. We conclude that GTE-EGCG modulates facial development with dose-dependent effects. Considering the potentially detrimental effects observed in mice, the therapeutic relevance of controlled GTE-EGCG administration towards reducing facial dysmorphology in young children with Down syndrome has yet to be confirmed by clinical studies.