Plasma Nuclear Magnetic Resonance Metabolomics Discriminates Between High and Low Endoscopic Activity and Predicts Progression in a Prospective Cohort of Patients With Ulcerative Colitis

Background and Aims: Endoscopic assessment of ulcerative colitis [UC] is one of the most accurate measures of disease activity, but frequent endoscopic investigations are disliked by patients and expensive for the healthcare system. A minimally invasive test that provides a surrogate measure of endoscopic activity is required. Methods: Plasma nuclear magnetic resonance [NMR] spectra from 40 patients with UC followed prospectively over 6 months were analysed with multivariate statistics. NMR metabolite profiles were compared with endoscopic [Ulcerative Colitis Endoscopic Index of Severity: UCEIS], histological [Nancy Index] and clinical [Simple Clinical Colitis Activity Index: SCCAI] severity indices, along with routine blood measurements. Results: A blinded principal component analysis spontaneously separated metabolite profiles of patients with low [<= 3] and high [>3] UCEIS. Orthogonal partial least squares discrimination analysis identified low and high UCEIS metabolite profiles with an accuracy of 77 +/- 5%. Plasma metabolites driving discrimination included decreases in lipoproteins and increases in isoleucine, valine, glucose and myo-inositol in high compared to low UCEIS. This same metabolite profile distinguished between low [Nancy 0-1] and high histological activity [Nancy 3-4] with a modest although significant accuracy [65 +/- 6%] but was independent of SCCAI and all blood parameters measured. A different metabolite profile, dominated by changes in lysine, histidine, phenylalanine and tyrosine, distinguished between improvement in UCEIS [decrease >= 1] and worsening [increase >= 1] over 6 months with an accuracy of 74 +/- 4%. Conclusion: Plasma NMR metabolite analysis has the potential to provide a low-cost, minimally invasive technique that may be a surrogate for endoscopic assessment, with predictive capacity.