Scientific Abstract
Proposal No. IBD-0187
Principal Investigator: Timothy Orchard, M.D.
Applicant Organization: Imperial College of Science, Technology and Medicine (London, United Kingdom)
Project Title: The use of metabonomic technology (nuclear magnetic resonance spectroscopy) in the investigation of Crohn’s disease
Period of Award: September 1, 2006 – August 31, 2009
The aims of this study are to test the following two hypotheses: 1) that urinary metabonomic profiles can be used to identify patients with Crohn’s disease (CD); and 2) that urinary metabonomic profiles in patients with CD are influenced by clinical phenotype, genotype and/or disease activity. This pilot study is a novel and exciting application of metabonomic technology to inflammatory bowel disease and, to our knowledge, the first attempt to use urinary nuclear magnetic resonance (NMR) spectroscopy in this context. Metabonomics describes the generation of metabolic information based on the analysis of biofluids or tissue samples, and provides an opportunity to identify specific biomarkers of disease dependent on underlying metabolic processes. High-resolution NMR spectroscopy of urine in combination with computer-based pattern recognition strategies provides information pertaining to physiology and disease. Analysis of urine samples has resulted in the identification of potential biomarkers for disease (in the form of distinctive NMR spectroscopic profiles) for a variety of conditions in humans.
The urinary metabolite profiles of patients with CD may be influenced by various factors. The most important are likely to be: a) the intestinal flora, which have particular relevance to urinary NMR spectroscopic profiling, and which have been shown to differ from that of healthy individuals; b) the presence of intestinal and/or systemic inflammation and c) the effect of increased intestinal permeability.
Given these differences, it is hypothesized that the NMR spectra of urine samples of CD patients differ significantly from those of normal subjects.
Urine samples will be analyzed from two highly selected groups of patients with CD and healthy controls. The first patient cohort will comprise patients with Crohn’s terminal ileitis, the second CD patients with type 1 (pauciarticular) peripheral arthritis. These groups have been chosen as they have been linked to abnormal responses to enteric bacteria and have particular genetic associations. Longitudinal sampling of the CD patients will be undertaken in remission and relapse, looking for variations in metabolic profile. Participants will be genotyped for HLA Class I and II and NOD2/CARD15 and these results will be available for stratification.
The proposed study to identify differences in metabonomic profile may yield biomarker profiles that provide novel insights into the pathogenesis of CD. Since the use of such techniques is non-invasive and the collection of urine samples acceptable to patients, this innovative approach may provide useful tools for the diagnosis and monitoring of inflammatory bowel disease.