High-throughput LC-FTMS and 1H-NMR for clinical metabolomics: Overcoming the barriers imposed by diet and diurnal variation

ANYL 209

Dean P Jones, dpjones@emory.edu1, Jennifer M Johnson, jmjohn8@emory.edu1, Frederick H Strobel, fstrobe@emory.edu2, Youngja Park, medyp@emory.edu1, Shaoxiong Wu, swu@emory.edu2, and Thomas R Ziegler, tzieg01@emory.edu1. (1) Department of Medicine, Emory University, 615 Michael Street, Suite 205P, Atlanta, GA 30322, (2) Department of Chemistry, Emory University, Atlanta, GA 30322
The human metabolome consists of metabolites generated endogenously from nutrients and common to all humans, as well as a vast xeno-metabolome derived from non-nutritive components of the diet. Studies with 1H-NMR spectroscopy and with HPLC coupled Thermo LTQ-FT hybrid ion-trap/Fourier-transform mass spectrometer, evaluated effects of diet and diurnal variation on the human plasma metabolome. 1H-NMR analyses measure mostly high concentration small molecules, and diurnal studies show that within day variations are large compared to differences between individuals at any time point. FTMS experiments have advantages over NMR in that they allow for higher sensitivity and specificity while allowing for easier automation. Principal component analyses showed that the metabolome of individuals consuming a chemically defined diet could be clearly separated from those consuming real food, indicating that investigations of the human metabolome can be simplified by consumption of a chemically defined diet prior to metabolomic sampling.