Scientific Abstract
Proposal No. IBD-0264R
Principal Investigator: Richard Neil Fedorak, M.D.
Applicant Organization: University of Alberta (Edmonton, Canada)
Project Title: The IBD metabolome project: human metabolomic analysis of patients with IBD
Period of Award: January 1, 2010 - March 31, 2013
We plan to develop a diagnostic tool based on metabolomics to not only distinguish CD and UC, but also to use this technology and the information gained to identify which patients are likely to have aggressive disease and those who will, or will not, respond to a specific treatment.
Objective: The objective of this research proposal is to generate preliminary data that will allow us to confirm the capacity of urine metabolomics to: 1) distinguish CD from UC and both of these inflammatory disorders from healthy controls; and 2) determine the relationship of disease activity and location in altering the metabolomic “fingerprint”.
Methods: Building on our expertise and success in other human inflammatory disorders and in identifying an IBD mouse urine metabolomic fingerprint, we will use 1H NMR analysis to examine urine from 240 patients with CD or UC (obtaining 3 samples per patient), and compare their metabolomic profiles to data from 240 non-IBD individuals which will include those with other inflammatory gastrointestinal conditions such as diverticulitis, infectious enteritis, and colitis. This process will develop a metabolomic “fingerprint” that will allow us to separate control from IBD patients, CD from UC, and correlate these results with disease activity. Disease activity will be characterized using the Harvey-Bradshaw Index questionnaire for CD patients, and a modified Mayo Clinic Score for UC patients. The NMR spectra obtained will be analyzed using the technique of targeted profiling, comparing spectra to a known reference database to identify metabolites. Statistical analysis using analysis of variance and Partial Least Squares Discriminant Analysis will be evoked to identify a metabolomic profile characteristic of CD or UC at various points during disease progression.
Summary: This project will provide the evidence for the use of urine metabolomics in human IBD and set the foundation for development of an accurate and cost effective diagnostic and surveillance test to distinguish between healthy individuals and those with IBD, and differentiate between patients with CD and UC. Within the IBD patients, we will link the metabolomic fingerprints with disease severity and location. Future research will correlate metabolomics with response to therapy and, later, potentially advance our understanding of the cause of IBD by examining the luminal microbe metabolites that could initiate and perpetuate human IBD.