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.