Abstract
Introduction
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.
Objectives
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’s disease (CD), and non-IBD subjects.
Methods
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).
Results
In total, 671 metabolites were identified. Comparing IBD and control subjects revealed 173 significantly altered metabolites (27 increased and 146 decreased). The majority of the alterations occurred in lipid-, amino acid-, and energy-related metabolites. Comparing only CD and control subjects revealed 286 significantly altered metabolites (54 increased and 232 decreased), whereas comparing UC and control subjects revealed only five significantly altered metabolites (all decreased). Hierarchal clustering using significant metabolites separated CD from UC and control subjects.
Conclusions
We demonstrate that a number of lipid-, amino acid-, and tricarboxylic acid cycle-related metabolites were significantly altered in IBD patients, more specifically in CD. Therefore, alterations in lipid and amino acid metabolism and energy homeostasis may play a key role in the pathogenesis of CD.
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Funding
Supported by National Institutes of Health (NIH) Grants R01AT004821 and 3R01AT004821-02S1 to KTW. EAS was supported by NIH Training Grant 2T32HD060554-06A1. LAC was supported by NIH Training Grant 5T32DK007673, a Vanderbilt Physician Scientist Development Award, a Veterans Affairs Career Development Award 1IK2BX002126, and a Vanderbilt Digestive Disease Research Center Pilot and Feasibility Award from NIH Grant P30DK058404. Additional support was provided by NIH Grant P30DK058404 (Vanderbilt Digestive Disease Research Center), NIH Grant UL1TR000445 (Vanderbilt CTSA), the Vanderbilt Hormone Assay & Analytical Services Core supported by NIH Grant P30DK020593 (Vanderbilt Diabetes Research and Training Center), NIH R01DK099204 and Veterans Affairs Merit Review Grant I01BX001426 to CSW, NIH Grants R01DK053620, R01CA190612, P01CA028842, P01CA116087, and Veterans Affairs Merit Review Grant I01BX001453 to KTW, and the Thomas F. Frist Sr. Endowment to KTW.
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David A. Schwartz has consultancy agreements with Abbvie, UCB, Janssen, Takeda, and Tigenix. Dawn B. Beaulieu has a consultancy agreement with Abbvie. Sara N. Horst has consultancy agreements with UCB and Salix. However, these agreements and grants had no relationship to the current research study. Keith T. Wilson has had a consulting agreement with Immune Pharmaceuticals. However, this agreement had no relationship to the current research study and is no longer active. The remainder of the authors declare that they have no conflict of interest.
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Scoville, E.A., Allaman, M.M., Brown, C.T. et al. Alterations in lipid, amino acid, and energy metabolism distinguish Crohn’s disease from ulcerative colitis and control subjects by serum metabolomic profiling. Metabolomics 14, 17 (2018). https://doi.org/10.1007/s11306-017-1311-y
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DOI: https://doi.org/10.1007/s11306-017-1311-y