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.

Fecal microbiota transplantation (FMT) has emerged as a highly effective therapy for recurrent Clostridioides difficile infection (rCDI) and also a potential therapy for other diseases associated with dysbiotic gut microbiota. Monitoring metabolic changes in biofluids and excreta is a noninvasive approach to identify the biomarkers of microbial recolonization and to understand the metabolic influences of FMT on the host. In this study, the pre-FMT and post FMT urine samples from 11 rCDI patients were compared through metabolomic analyses for FMT-induced metabolic changes. The results showed that p-cresol sulfate in urine, a microbial metabolite of tyrosine, was rapidly elevated by FMT and much more responsive than other microbial metabolites of aromatic amino acids (AAAs). Because patients were treated with vancomycin prior to FMT, the influence of vancomycin on the microbial metabolism of AAAs was examined in a mouse feeding trial, in which the decreases in p-cresol sulfate, phenylacetylglycine, and indoxyl sulfate in urine were accompanied with significant increases in their AAA precursors in feces. The inhibitory effects of antibiotics and the recovering effects of FMT on the microbial metabolism of AAAs were further validated in a mouse model of FMT. Overall, urinary p-cresol sulfate may function as a sensitive and convenient therapeutic indicator on the effectiveness of antibiotics and FMT for the desired manipulation of gut microbiota in human patients.