Lay Summary
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 aim of this research project is to evaluate the use of an innovative technique, metabonomics, for the diagnosis and monitoring of Crohn’s disease (CD). The specific questions that we shall address are: Can the use of metabonomic technology in analyzing urine samples identify patients with CD? Can subgroups of CD patients be distinguished by these means? And can this technique identify when the disease flares up?
‘Metabonomics’ describes the generation of an individualized ‘barcode’ that reflects a person’s underlying metabolic processes from the analysis of tissue samples or bodily fluids such as urine.
Recently this technique has been applied to human diseases such as osteoarthritis, polymyositis, dermatomyositis and malabsorption syndromes. The study of urine samples from patients with these conditions has shown that these diseases are associated with specific barcode patterns. As the individual components of each barcode can be identified, this offers the possibility of identifying very specific biological markers of disease. This may be of great potential benefit in diagnosis and disease evaluation.
Our study will examine urine samples from Crohn’s patients and normal individuals. Metabonomic profiles will be generated using a technique called nuclear magnetic resonance (NMR) spectroscopy.
There are several reasons why it is likely that unique profiles will be found in CD. The human gastrointestinal tract contains many different species of bacteria, and it has been shown that these differ between CD and normal subjects. It has recently been shown that the gut bacteria play a very important role in the generation of an individual’s urinary metabonomic profiles, as they are involved in many metabolic processes. So there is a high chance that differences in these bacteria in patients with CD may cause significant distinguishing features in their urinary profiles. The increased inflammation and intestinal permeability associated with CD may also contribute to differences.
Two subgroups of CD patients, those with ileal inflammation and joint problems, will be studied to see if they can be differentiated from healthy people. These have been chosen because of specific genetic associations and associations with an abnormal response to gut bacteria. Urine samples will also be analyzed when the disease is in remission and is flaring, looking for any differences.
The methodology, if effective, will provide an important, patient-acceptable way of identifying and investigating CD and there may be future implications for disease monitoring. The identification of the metabolites within the barcode may also yield novel insights into the causes of CD.
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.