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

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 characterize the metabolic changes during management of patients with tumor 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 analyzed by 1H nuclear magnetic resonance (NMR) spectroscopy. Data were analyzed 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 (UC) and controls, active Crohn’s disease (CD) and controls, and quiescent CD 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 potential 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. and Wwith its use we provide unique insights into the metabolic changes taking place during induction treatment with IFX is provided. 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.