Bimodal plasma metabolomics strategy identifies novel inflammatory metabolites in inflammatory bowel diseases

Yunki Y. Yau, Rupert W. L. Leong, Sean Shin, Sonia Bustamante, Russell Pickford, Leila Hejazi, Beth Campbell, Valerie C. Wasinger*

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Introduction: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterized by variable phenotypes. Metabolites are signatures of biochemical activity that can reveal unknown pathogenic pathways. We employed untargeted mass spectrometry (MS) based metabolomics to identify novel inflammatory mechanisms in IBD and a targeted assay to quantify metabolites of the auto-immunomodulating kynurenine pathway (KP) in IBDs and health. Materials and Methods: Metabolome analysis of CD, UC, and control plasmas was performed on a Liquid Chromatography (LC)-MS/MS system. KP metabolites quinolinic acid (QA) and picolinic acid (PA) were quantified by gas chromatography/MS. Results: Nineteen UC, 25 CD, and 9 control plasmas were analyzed: 34 metabolites exhibited abundance profiles associated with CD by global metabolome analysis (P=0.05, false discovery rate q=0.01). Notably, inflammatory-implicated metabolites angiotensin IV (P=0.049, q<0.001), diphthamide (P=0.018, q<0.001), and GM3 gangliosides (P<0.001, q<0.001) were increased in CD. By targeted kynurenine metabolites assay, QA (73.53 ng/mL ± 23.40 SD) and combined kynurenine metabolites (CKM) were increased in CD (120.19 ± 39.71) compared to controls (QA 50.14 ± 15.04; P<0.01; CKM 92.73 ± 26.30; P<0.01). CD QA positively correlated with CDAI (r=0.85; P<0.01), CRP (r=0.46; P=0.01), and ESR (r=0.42; P=0.03), while CKMs correlated with CDAI (r=0.615; P<0.01) and CRP (r=0.615; P=0.02). Conclusions: Associations of angiotensin IV, diphthamide, and GM3 gangliosides with CD implicate novel pathways in activating a Th1/Th17 inflammatory profile. Increased QA concentrations in CD may indicate a defective auto-immunomodulation mechanism.

Original languageEnglish
Pages (from-to)113-124
Number of pages12
JournalDiscovery medicine
Volume18
Issue number98
Publication statusPublished - 2014
Externally publishedYes

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Yau, Y. Y., Leong, R. W. L., Shin, S., Bustamante, S., Pickford, R., Hejazi, L., ... Wasinger, V. C. (2014). Bimodal plasma metabolomics strategy identifies novel inflammatory metabolites in inflammatory bowel diseases. Discovery medicine, 18(98), 113-124.