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01.12.2017 | Research article | Ausgabe 1/2017 Open Access

BMC Medicine 1/2017

Metabonomics uncovers a reversible proatherogenic lipid profile during infliximab therapy of inflammatory bowel disease

Zeitschrift:
BMC Medicine > Ausgabe 1/2017
Autoren:
Jacob Tveiten Bjerrum, Casper Steenholdt, Mark Ainsworth, Ole Haagen Nielsen, Michelle AC Reed, Karen Atkins, Ulrich Leonhard Günther, Fuhua Hao, Yulan Wang
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12916-017-0949-7) contains supplementary material, which is available to authorized users.

Abstract

Background

One-third of inflammatory bowel disease (IBD) patients show no response to infliximab (IFX) induction therapy, and approximately half of patients responding become unresponsive over time. Thus, identification of potential treatment response biomarkers are of great clinical significance. This study employs spectroscopy-based metabolic profiling of serum from patients with IBD treated with IFX and healthy subjects (1) to substantiate the use of spectroscopy as a semi-invasive diagnostic tool, (2) to identify potential biomarkers of treatment response and (3) to characterise the metabolic changes during management of patients with tumour necrosis factor-α inhibitors.

Methods

Successive serum samples collected during IFX induction treatment (weeks 0, 2, 6 and 14) from 87 IBD patients and 37 controls were analysed by 1H nuclear magnetic resonance (NMR) spectroscopy. Data were analysed with principal components analysis and orthogonal projection to latent structures discriminant analysis using SIMCA-P+ v12 and MATLAB.

Results

Metabolic profiles were significantly different between active ulcerative colitis and controls, active Crohn’s disease and controls, and quiescent Crohn’s disease and controls. Metabolites holding differential power belonged primarily to lipids and phospholipids with proatherogenic characteristics and metabolites in the pyruvate metabolism, suggestive of an intense inflammation-driven energy demand. IBD patients not responding to IFX were identified as a potentially distinct group based on their metabolic profile, although no applicable response biomarkers could be singled out in the current setting.

Conclusion

1H NMR spectroscopy of serum samples is a powerful semi-invasive diagnostic tool in flaring IBD. With its use, we provide unique insights into the metabolic changes taking place during induction treatment with IFX. Of distinct clinical relevance is the identification of a reversible proatherogenic lipid profile in IBD patients with active disease, which partially explains the increased risk of cardiovascular disease associated with IBD.
Zusatzmaterial
Additional file 1: Figure S1. 1H NMR spectra of serum and metabolite assignment. (DOCX 116 kb)
12916_2017_949_MOESM1_ESM.docx
Additional file 2: Table S1. Number of subjects and serum samples. (DOCX 18 kb)
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Additional file 3: Figure S2. Area under the receiver operating characteristic (ROC) curve. (DOCX 211 kb)
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Additional file 4: Table S2. Validation of PLS-DA and O-PLS-DA models. (DOCX 24 kb)
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Additional file 5: Tables S3. Validation of PLS-DA and O-PLS-DA models of UC phenotypes and treatment response. (DOCX 23 kb)
12916_2017_949_MOESM5_ESM.docx
Additional file 6: Tables S4. Validation of PLS-DA and O-PLS-DA models of CD phenotypes and treatment response. (DOCX 24 kb)
12916_2017_949_MOESM6_ESM.docx
Additional file 7: Figure S3. Correlation analysis between phenylalanine and tyrosine. (DOCX 49 kb)
12916_2017_949_MOESM7_ESM.docx
Literatur
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