These authors equally contributed to the manuscript.Dietary polyphenols in tea and wine have been associated with beneficial health effects. After ingestion, most polyphenols are metabolized by the colonic microbiota. The current study aimed at exploring the interindividual variation of gut microbial polyphenol bioconversion from 10 healthy human subjects. In vitro fecal batch fermentations simulating conditions in the distal colon were performed using polyphenols from black tea and a mixture of red wine and grape juice. Microbial bioconversion was monitored by NMR-and GC-MS-based profiling of diverse metabolites and phenolics. The complex polyphenol mixtures were degraded to a limited number of key metabolites. Each subject displayed a specific metabolite profile differing in composition and time courses as well as levels of these metabolites. Moreover, clear differences depending on the polyphenol sources were observed. In conclusion, varying metabolite pathways among individuals result in different metabolome profiles and therefore related health effects are hypothesized to differ between subjects.

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Gut microbial catabolites of black tea polyphenols (BTPs) have been proposed to exert beneficial cardiovascular bioactivity. This hypothesis is difficult to verify because the conjugation patterns and pharmacokinetics of these catabolites are largely unknown. The objective of our study was to identify, quantify, and assess the pharmacokinetics of conjugated BTP metabolites in plasma of healthy humans by means of an a priori untargeted LC-MS-based metabolomics approach. In a randomized, open, placebo-controlled, crossover study, 12 healthy men consumed a single bolus of black tea extract (BTE) or a placebo. The relative and, in several cases, absolute concentrations of a wide range of metabolites were determined using U(H)PLC-LTQ-Orbitrap-FTMS. Following BTE consumption, a kinetic response in plasma was observed for 59 BTP metabolites, 11 of these in a quantitative manner. Conjugated and unconjugated catechins appeared in plasma without delay, at 2-4 h, followed by a range of microbial catabolites. Interindividual variation in response was greater for gut microbial catabolites than for directly absorbed BTPs. The rapid and sustained circulation of conjugated catabolites suggests that these compounds may be particularly relevant to proposed health benefits of BTE. Their presence and effects may depend on individual variation in catabolic capacity of the gut microbiota.