Serum and urine metabolomic fingerprinting in diagnostics of inflammatory bowel diseases

• Published in: World journal of gastroenterology : WJG 2014-01, Vol.20 (1), p.163-174
• Main Author: Dawiskiba, Tomasz
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Area Under Curve; Biomarkers - blood; Biomarkers - urine; bowel; Case-Control Studies; Colitis, Ulcerative - blood; Colitis, Ulcerative - diagnosis; Colitis, Ulcerative - therapy; Colitis, Ulcerative - urine; Crohn Disease - blood; Crohn Disease - diagnosis; Crohn Disease - therapy; Crohn Disease - urine; Diagnosis, Differential; Discriminant Analysis; disease; Female; Humans; Inflammatory; Least-Squares Analysis; Magnetic Resonance Spectroscopy; Male; Metabolomics; Metabolomics - methods; Middle Aged; Original; Poland; Predictive Value of Tests; Prognosis; Remission Induction; ROC Curve; Severity of Illness Index; Ulcerative; Young Adult
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v20.i1.163

AIM:To evaluate the utility of serum and urine metabolomic analysis in diagnosing and monitoring of inflammatory bowel diseases(IBD).METHODS:Serum and urine samples were collected from 24 patients with ulcerative colitis(UC),19 patients with the Crohn’s disease(CD)and 17 healthy controls.The activity of UC was assessed with the Simple Clinical Colitis Activity Index,while the activity of CD was determined using the Harvey-Bradshaw Index.The analysis of serum and urine samples was performed using proton nuclear magnetic resonance(NMR)spectroscopy.All spectra were exported to Matlab for preprocessing which resulted in two data matrixes for serum and urine.Prior to the chemometric analysis,both data sets were unit variance scaled.The differences in metabolite fingerprints were assessed using partial least-squaresdiscriminant analysis(PLS-DA).Receiver operating characteristic curves and area under curves were used to evaluate the quality and prediction performance of the obtained PLS-DA models.Metabolites responsible for separation in models were tested using STATISTICA10 with the Mann-Whitney-Wilcoxon test and the Student’s t test(α=0.05).RESULTS:The comparison between the group of patients with active IBD and the group with IBD in remission provided good PLS-DA models(P value 0.002for serum and 0.003 for urine).The metabolites that allowed to distinguish these groups were:N-acetylated compounds and phenylalanine(up-regulated in serum),low-density lipoproteins and very low-density lipoproteins(decreased in serum)as well as glycine(increased in urine)and acetoacetate(decreased in urine).The significant differences in metabolomic profiles were also found between the group of patients with active IBD and healthy control subjects providing the PLS-DA models with a very good separation(P value<0.001 for serum and 0.003 for urine).The metabolites that were found to be the strongest biomarkers included in this case:leucine,isoleucine,3-hydroxybutyric acid,N-acetylated compounds,acetoacetate,glycine,phenylalanine and lactate(increased in serum),creatine,dimethyl sulfone,histidine,choline and its derivatives(decreased in serum),as well as citrate,hippurate,trigonelline,taurine,succinate and 2-hydroxyisobutyrate(decreased in urine).No clear separation in PLS-DA models was found between CD and UC patients based on the analysis of serum and urine samples,although one metabolite(formate)in univariate statistical analysis was significantly lower in serum of patients wit