Magic angle spinning NMR and 1H-31P heteronuclear statistical total correlation spectroscopy of intact human gut biopsies.
Previously we have demonstrated the use of 1H magic angle spinning (MAS) NMR spectroscopy for the topographical variations in functional metabolic signatures of intact human intestinal biopsy samples. Here we have analyzed a series of MAS 1H NMR spectra (spin-echo, one-dimensional, and diffusion-edited) and 31P-{1H} spectra and focused on analyzing the enhancement of information recovery by use of the statistical total correlation spectroscopy (STOCSY) method. We have applied a heterospectroscopic cross-examination performed on the same samples and between 1H and 31P-{1H} spectra (heteronuclear STOCSY) to recover latent metabolic information. We show that heterospectroscopic correlation can give new information on the molecular compartmentation of metabolites in intact tissues, including the statistical "isolation" of a phospholipid/triglyceride vesicle pool in intact tissue. The application of 31P-1H HET-STOCSY allowed the cross-assignment of major 31P signals to their equivalent 1H NMR spectra, e.g., for phosphorylcholine and phosphorylethanolamine. We also show pathway correlations, e.g., the ascorbate-glutathione pathway, in the STOCSY analysis of intact tissue spectra. These 31P-1H HET-STOCSY spectra also showed different topographical regions, particular for minor signals in different tissue microenvironments. This approach could be extended to allow the detection of altered distributions within metabolic subcompartments as well as conventional metabonomics concentration-based diagnostics.
Wang
Yulan
Y
Department of Biomolecular Medicine, SORA Division, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, South Kensington, London, UK. yulan.wang@imperial.ac.uk
Cloarec
Olivier
O
Tang
Huiru
H
Lindon
John C
JC
Holmes
Elaine
E
Kochhar
Sunil
S
Nicholson
Jeremy K
JK
D001205:Ascorbic Acid / Q000378:metabolism; D001706:Biopsy; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000473:pathology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D010743:Phospholipids / Q000378:metabolism; D010759:Phosphorus Isotopes / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013113:Spin Labels; D013223:Statistics as Topic; D014280:Triglycerides / Q000378:metabolism
D010743:Phospholipids; D010759:Phosphorus Isotopes; D013113:Spin Labels; D014280:Triglycerides; D005978:Glutathione; D001205:Ascorbic Acid