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Sunday, October 17, 2010

Metabolomics

TRYPTOPHAN METABOLOMICS DIFFERENTIATES IN INFLAMMATORY BOWEL DISEASES.
Bustamante S, Pickford R, Shin S, Luber R, Campbell B, Redmond D, Yau Y, Leong RWL, Wasinger V. Gastroenterology and Liver Services, Concord and Bankstown Hospitals, Sydney; Bioanalytical Mass Spectrometry Facility, The University of New South Wales.
BACKGROUND & AIM: Metabolomics is the physiological study of chemical profiles of specific metabolic processes. The plasma metabolome in IBD has not been previously characterised. Indoleamine 2,3-dioxygenase (IDO) suppresses naïve T cell proliferation by inducing their apoptosis through tryptophan catabolism, which produces the end metabolites quinolinic acid (QA) and picolinic acid (PA). Whether their role in maintaining tolerance is impaired in inflammatory bowel disease (IBD), or if it differentiates Crohn's disease (CD) from ulcerative colitis (UC) and controls, is unknown.
METHODS: Quantitative metabolomics of picolinic and quinolinic acid was performed using gas chromatography/ mass spectrometry (GC/MS) on blinded CD, UC and control plasma. GC/MS was performed on a HP 6890 gas chromatograph interfaced to a mass selective detector. Analysis was performed with the mass spectrometer operating in electron-capture, negative-ion mode, using methane as reagent gas. We have also used a non-targeted approach to explore small molecule metabolites present in IBD plasma to determine if disease state can be linked to physiological changes. Whole metabolome (mass 50 to 1000m/z) was analysed using an Orbitrap MS instrument. SIEVE software (ThermoFisher Scientific) was used to quantitate, while ChemSpider search engine was used to identify the chemical compounds.
RESULTS: Nineteen UC, 16 CD and 9 controls were recruited. QA and PA levels were increased in UC and CD compared to controls with CD reaching statistical significance (P=0.007 for QA and P=0.004 for total metabolite). Both QA and PA increased with CD inflammation (P=0.015 for QA and P=0.006 for total metabolite). Non-targeted metabolomic study revealed a large number of metabolites differentially expressed.
CONCLUSIONS: Plasma metabolomics demonstrated differences in tryptophan metabolism between CD and UC and controls. Additionally, deficiency fatty acid metabolism linked to APO lipoproteins may be a co-factor in peroxisome dysfunction and linked to defects in autophagy in CD.  

AGW Next Week

Two presentations - poster on Metabolomics in IBD and confocal endomicroscopy in IBD.