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Metabolomic Profiling in Inflammatory Bowel Disease
[Thesis]. Manchester, UK: The University of Manchester; 2014.
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Abstract
AbstractThe University of Manchester Colette JohnstonDegree of Doctor of MedicineMetabolomics Profiling in Inflammatory Bowel Disease13th Feb 2014IntroductionInflammatory bowel disease is a common, complex relapsing disorder characterised by immune dysregulation, altered intestinal permeability and microbial insult. Limited knowledge is available regarding the metabolic changes observed during progression of the disease, and limited biomarkers of disease available that have been validated and shown to be of sound clinical value.Aim of StudyA two stage metabolomics approach was adopted to determine if metabolic signature profiles, could distinguish inflammatory bowel disease Crohn’s disease (CD) patients from ulcerative colitis (UC) patients and from healthy controls.MethodsA serum metabolomics approach was undertaken to define metabolic changes associated with UC and CD. Serum samples from a discovery study of 30 UC, 30 CD and 29 ethnically, age and gender matched controls were analysed by ultra-performance liquid chromatography mass spectrometry. A subsequent validation study was preformed using 28UC, 31CD, and 29 gender matched controls were also analysed using UPLC-MS.ResultsClasses of metabolites, identified as biologically interesting and at significantly different levels (p<0.05) in comparisons of control and CD and UC cohorts included: steroids and steroid derivatives, phosphocholine, Vitamin D metabolites, fatty acids and conjugates, glycerolipids, isoprenoids, amino acids, and phosphosphingolipids. There were fewer discriminatory metabolites differentiating the CD and UC cohorts. ConclusionSerum Metabolomic profiling may represent a novel technology which could be used to distinguish individuals with CD from those with UC and healthy controls.