Phenotyping Tea Consumers by Nutrikinetic Analysis of Polyphenolic End-Metabolites

An integration of metabolomics and pharmacokinetics (or nutrikinetics) is introduced as a concept to describe a human study population with different metabolic phenotypes following a nutritional intervention. The approach facilitates an unbiased analysis of the time-response of body fluid metabolites from crossover designed intervention trials without prior knowledge of the underlying metabolic pathways. The method is explained for the case of a human intervention study in which the nutrikinetic analysis of polyphenol-rich black tea consumption was performed in urine over a period of 48 h. First, multilevel PLS-DA analysis was applied to the urinary 1H NMR profiles to select the most differentiating biomarkers between the verum and placebo samples. Then, a one-compartment nutrikinetic model with first-order excretion, a lag time, and a baseline function was fitted to the time courses of these selected biomarkers. The nutrikinetic model used here fully exploits the crossover structure in the data by fitting the data from both the treatment period and the placebo period simultaneously. To demonstrate the procedure, a selected set of urinary biomarkers was used in the model fitting. These metabolites include hippuric acid, 4-hydroxyhippuric acid and 1,3-dihydroxyphenyl-2-O-sulfate and derived from microbial fermentation of polyphenols in the gut. Variations in urinary excretion between- and within the subjects were observed, and used to provide a phenotypic description of the test population.