Abstract

The bioactivities and potential health benefits of green tea polyphenols (GTP) have been extensively investigated, but the metabolic impact of chronic GTP intake on humans is not well defined. In this study, fecal and urine samples from postmenopausal female subjects taking a GTP supplement or placebo for 12 months were compared by liquid chromatography-mass spectrometry-based metabolomic analysis. The GTP-derived and GTP-responsive metabolites were identified and characterized by structural elucidation and quantitative analysis of the metabolites contributing to the separation of control and treatment samples in the multivariate models. Major GTP and their direct sulfate and glucuronide metabolites were absent in feces and urine. In contrast, GTP-derived phenyl-γ-valerlactone and phenylvaleric acid metabolites were identified as the most abundant GTP-derived metabolites in feces and urine, suggesting extensive microbial biotransformation of GTP in humans. Interestingly, GTP decreased the levels of microbial metabolites of aromatic amino acids (AAA), including indoxyl sulfate, phenylacetylglutamine, and hippuric acid, in urine. However, it did not affect the levels of AAA, as well as other microbial metabolites, including short-chain fatty acids and secondary bile acids, in feces. 16S rRNA gene sequencing indicated that the fecal microbiome was not significantly affected by chronic consumption of GTP. Overall, microbial metabolism is responsible for the formation of GTP metabolites while GTP metabolism may inhibit the formation of AAA metabolites from microbial metabolism. Because these GTP-derived and GTP-responsive metabolites have diverse bioactivities, microbial metabolism of GTP and AAA may play important roles in the beneficial health effects of green tea consumption in humans.

Highlights

  • Tea (Camellia sinensis) is the second most consumed beverage in the world after water [1].Green tea, as unfermented tea leaf, contains green tea polyphenols (GTP), which are a series of catechins

  • GTP are hydrophilic and the substrates of efflux intestinal transporters [3]. These properties limit the bioavailability of GTP by decreasing the absorption in the small intestine and increasing the biliary excretion in the liver. This was confirmed by the fact that only trace amounts of EGCG and ECG were detected in the circulatory system after green tea consumption, and substantial quantities of GTP passed through the small intestine unabsorbed when analyzing ileal

  • Subtle changes in fecal metabolome were observed based on the separation of T12 group from T0, P0, and P12 groups in the scores plot of a supervised partial least squares-discriminant analysis (PLS-DA) model (Figure 1A)

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Summary

Introduction

Tea (Camellia sinensis) is the second most consumed beverage in the world after water [1].Green tea, as unfermented tea leaf, contains green tea polyphenols (GTP), which are a series of catechins (flavan-3-ols). GTP are hydrophilic and the substrates of efflux intestinal transporters [3]. These properties limit the bioavailability of GTP by decreasing the absorption in the small intestine and increasing the biliary excretion in the liver. This was confirmed by the fact that only trace amounts of EGCG and ECG were detected in the circulatory system after green tea consumption, and substantial quantities of GTP passed through the small intestine unabsorbed when analyzing ileal

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