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Alterations in Lipid, Amino Acid, and Energy Metabolism Distinguish Crohn Disease from Ulcerative Colitis and Control Subjects by Serum Metabolomic Profiling

ABSTRACT: Non-invasive biomarkers are needed in inflammatory bowel disease (IBD) to help define disease activity and identify underlying pathogenic mechanisms. We hypothesized that serum metabolomics, which produces unique metabolite profiles, can aid in this search. The aim of this study was to characterize serum metabolomic profiles in patients with IBD, and to assess for differences between patients with ulcerative colitis (UC), Crohn disease (CD), and non-IBD subjects. Serum samples from 20 UC, 20 CD, and 20 non-IBD control subjects were obtained along with patient characteristics, including medication use and clinical disease activity. Non-targeted metabolomic profiling was performed using ultra-high performance liquid chromatography/mass spectrometry (UPLC-MS/MS) optimized for basic or acidic species and hydrophilic interaction liquid chromatography (HILIC/UPLC-MS/MS).

ORGANISM(S): Human Homo Sapiens

TISSUE(S): Blood

DISEASE(S): Inflammatory Bowel Disease

SUBMITTER: Elizabeth Scoville

PROVIDER: ST000899 | MetabolomicsWorkbench | Tue Aug 29 00:00:00 BST 2017

REPOSITORIES: MetabolomicsWorkbench

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Project description:Inflammatory bowel disease (IBD) is a complex multi-factorial inflammatory disease with Crohn’s disease (CD) and ulcerative colitis (UC) being the two most common forms. A number of transcriptional profiling studies have provided compelling evidence that describe the role of protein-coding genes and microRNAs in modulating the immune responses in IBD. In the present study, we performed a genome-wide transcriptome profiling of lncRNAs and protein-coding genes in inflamed and non-inflamed colon pinch biopsies from the IBD patients using expression microarrays platform. In this study, we identified widespread dysregulation of lncRNAs and protein-coding genes in both inflamed and non-inflamed CD and UC compared to the healthy controls. In case of inflamed CD and UC (iCD and iUC), we identified 438 and 745 differentially expressed lncRNAs, respectively, while in case of the non-inflamed CD and UC (niCD and niUC), we identified 12 and 19 differentially expressed lncRNAs, respectively. We also observed significant enrichment (p-value < 0.001, Pearson’s Chi-squared test) for 96 differentially expressed lncRNAs and 154 protein-coding genes within the IBD susceptibility loci. Furthermore, we found strong positive expression correlations for the intersecting and cis-neighboring differentially expressed IBD loci-associated lncRNA-protein-coding gene pairs. The functional annotation analysis of differentially expressed genes revealed that they are involved in immune response, pro-inflammatory cytokine activity and MHC protein complex. The lncRNA expression profiling in both inflamed and non-inflamed CD and UC, successfully stratified IBD patients from the healthy controls. Taken together, the identified lncRNA transcriptional signature along with clinically relevant parameters suggests their potential as biomarkers in IBD. A total of 96 biopsy samples (including 6 samples used as technical replicates) extracted from different colonic locations from 45 patients (CD=13, UC=20, Controls=12) were profiled using Agilent Custom 8x60K format lncRNA expression microarray. In Gencode v15 lncRNA microarray design, each lncRNA transcript is targeted by two probes covering 22,001 lncRNA transcripts corresponding to 12,963 lncRNA genes. In addition, each array contains 17,535 randomly-selected protein-coding targets, of which 15,182 (unique 12,787) correspond to protein-coding genes.

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Alterations in Lipid, Amino Acid, and Energy Metabolism Distinguish Crohn Disease from Ulcerative Colitis and Control Subjects by Serum Metabolomic Profiling

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