ORIGINAL ARTICLE Population-based nutrikinetic modeling of polyphenol exposure Ewoud J. J. van Velzen • Johan A. Westerhuis • Christian H. Gru ¨n • Doris M. Jacobs • Paul H. C. Eilers • Theo P. Mulder • Martin Foltz • Ursula Garczarek • Rober Kemperman • Elaine E. Vaughan • John P. M. van Duynhoven • Age K. Smilde Received: 4 November 2013 / Accepted: 22 February 2014 Ó Springer Science+Business Media New York 2014 Abstract The beneficial health effects of fruits and veg- etables have been attributed to their polyphenol content. These compounds undergo many bioconversions in the body. Modeling polyphenol exposure of humans upon intake is a prerequisite for understanding the modulating effect of the food matrix and the colonic microbiome. This modeling is not a trivial task and requires a careful inte- gration of measuring techniques, modeling methods and experimental design. Moreover, both at the population level as well as the individual level polyphenol exposure has to be quantified and assessed. We developed a strategy to quantify polyphenol exposure based on the concept of nutrikinetics in combination with population-based mod- eling. The key idea of the strategy is to derive nutrikinetic model parameters that summarize all information of the polyphenol exposure at both individual and population level. This is illustrated by a placebo-controlled crossover study in which an extract of wine/grapes and black tea solids was administered to twenty subjects. We show that urinary and plasma nutrikinetic time-response curves can be used for phenotyping the gut microbial bioconversion capacity of individuals. Each individual harbours an intrinsic microbiota composition converting similar poly- phenols from both test products in the same manner and stable over time. We demonstrate that this is a novel approach for associating the production of two gut-medi- ated c-valerolactones to specific gut phylotypes. The large inter-individual variation in nutrikinetics and c-valerolac- tones production indicated that gut microbial metabolism is an essential factor in polyphenol exposure and related potential health benefits. Keywords Black tea  Grapes  HPLC  Human intestinal tract chip  Microbiota  NMR  Nutrikinetics  Nutrition  Pharmacokinetics  Phylogenetic analysis  Red wine  Valerolactones 1 Introduction There is ample epidemiological evidence for the beneficial health effects of fruits and vegetables. A large number of in vivo and in vitro studies point towards involvement of polyphenols as a major class of responsible bioactive compounds. Despite decades of research effort, attempts to establish exposure-effect relationships for the polyphenols Electronic supplementary material The online version of this article (doi:10.1007/s11306-014-0645-y) contains supplementary material, which is available to authorized users. E. J. J. van Velzen  J. A. Westerhuis  A. K. Smilde (&) Biosystems Data Analysis, University of Amsterdam, P.O. Box 94215, 1090 GE, Amsterdam, The Netherlands e-mail: a.k.smilde@uva.nl E. J. J. van Velzen  C. H. Gru ¨n  D. M. Jacobs  T. P. Mulder  M. Foltz  U. Garczarek  R. Kemperman  E. E. Vaughan  J. P. M. van Duynhoven Unilever Research and Development, Vlaardingen, The Netherlands E. J. J. van Velzen  J. A. Westerhuis  D. M. Jacobs  J. P. M. van Duynhoven  A. K. Smilde Netherlands Metabolomics Centre, Leiden, The Netherlands P. H. C. Eilers Department of Biostatistics, Erasmus University Medical Centre, Rotterdam, The Netherlands J. P. M. van Duynhoven Laboratory of Biophysics, Wageningen University, Wageningen, The Netherlands 123 Metabolomics DOI 10.1007/s11306-014-0645-y