TY - JOUR
T1 - Metabonomics uncovers a reversible proatherogenic lipid profile during infliximab therapy of inflammatory bowel disease
AU - Bjerrum, Jacob Tveiten
AU - Steenholdt, Casper
AU - Ainsworth, Mark
AU - Nielsen, Ole Haagen
AU - Reed, Michelle A.C.
AU - Atkins, Karen
AU - Günther, Ulrich Leonhard
AU - Hao, Fuhua
AU - Wang, Yulan
N1 - Funding Information:
We acknowledge NMR access to spectrometers at HWB-NMR (Birmingham), supported by the European Union, FP7-INFRA-2010-1.1.8-261863 Bio-NMR. Michelle A. C. Reed was also supported in part by a COSMOS EU grant (FP7-INFRA-2012-1-312941).
Publisher Copyright:
© 2017 The Author(s).
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2017/10/16
Y1 - 2017/10/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85031408391&partnerID=8YFLogxK
U2 - 10.1186/s12916-017-0949-7
DO - 10.1186/s12916-017-0949-7
M3 - Journal articles
C2 - 29032767
AN - SCOPUS:85031408391
SN - 1741-7015
VL - 15
JO - BMC Medicine
JF - BMC Medicine
IS - 1
M1 - 184
ER -
