Multicompartmental LC-Q-TOF-Based Metabonomics as an Exploratory Tool to Identify Novel Pathways Affected by Polyphenol-Rich Diets in Mice

Metabonomics has recently been used to study the physiological response to a given nutritional intervention, but such studies have usually been restricted to changes in either plasma or urine. In the present study, we demonstrate that the use of LC-Q-TOF-based metabolome analyses (foodstuff, plasma, urine, and caecal content metabolomes) in mice offer higher order information, including intra- and intercompartment relationships. To illustrate this, we performed an intervention study with three different phenolic-rich extracts in mice over 3 weeks. Both unsupervised (PCA) and supervised (PLS-DA) multivariate analyses used for pattern recognition revealed marked effects of diet in each compartment (plasma, urine, and caecal contents). Specifically, dietary intake of phenolic-rich extract affects pathways such as bile acid and taurine metabolism. Q-TOF-based metabonomics demonstrated that the number of correlations is higher in caecal contents and urine than in plasma. Moreover, intercompartment correlations showed that caecal contents–plasma correlations are the most frequent in mice, followed by plasma–urine ones. The number of inter- and intracompartment correlations is significantly affected by diet. These analyses reveal the complexity of interorgan metabolic relationships and their sensitivity to dietary changes.