Untargeted metabolomics identifies potential serum biomarkers associated with Crohn's disease.

Abstract

Crohn's disease (CD) is well characterized by chronic inflammation of the gastrointestinal tract. The diagnose of CD relays on the comprehensive evaluation of patient symptoms, laboratory examination, radiology, and endoscopy. There is lack of biomarkers or simple test for CD detection. Serum samples from healthy subjects (n = 16) and CD patients (n = 16) were collected and prepared for untargeted metabolomics analysis using the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) method. The alterations of serum metabolites and the potential biomarkers were profiled by statistical analysis. And the associated metabolic pathway was analyzed based on Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The performance of potential biomarkers was assessed by receiver operating characteristic (ROC) analysis. A complete separation between HS and CD groups was seen in OPLS-DA. A total of 108 and 131 significantly altered metabolites in positive and negative ion mode, respectively, were identified, and most of them belong to several pathways ranging from lipid metabolism to amino acid metabolism and energy homeostasis. KEGG analysis revealed that lipid metabolism enriched most significantly. Further, ceramide, phosphatidylethanolamine (PE), and taurochenodeoxycholic acid (TCDCA) presented the highest predictive accuracy of the patients with CD as analyzed by ROC. The current study demonstrated that lipid metabolism is mostly related to CD pathogenesis. Further investigations are indicated to examine the use of lipid-related metabolites of ceramide, PE, and TCDCA as potential biomarkers for CD diagnosis.