Background: A distinctive metabolic phenotype provides the opportunity to discover noninvasive biomarkers for the diagnosis of Crohn's disease (CD) and for differentiating it from other intestinal inflammatory diseases. The study sought to identify new biomarkers for CD diagnosis.
Methods: Serum metabolites from 68 newly diagnosed and treatment-naïve patients with CD and 56 healthy control (HC) subjects were profiled using targeted liquid chromatography-mass spectrometry. Five metabolic biomarkers were identified to distinguish patients with CD from the HC subjects and validated in a separate cohort consisting of 110 patients with CD and 90 HC subjects using a combination of univariate analysis, orthogonal partial least-squares discriminant analysis, and receiver-operating characteristic curve analysis. Differences in the 5 metabolites were evaluated among patients with CD and patients with ulcerative colitis (n = 62), intestinal tuberculosis (n = 48), and Behçet's disease (n = 31).
Results: Among the 185 quantified metabolites, a panel of 5 (pyruvate, phenylacetylglutamine, isolithocholic acid, taurodeoxycholic acid, and glycolithocholic acid) were found to distinguish patients with CD with high accuracy from HC subjects, with an area under the curve of 0.861 (P < .001). The performance of the model in assessing clinical disease activity was comparable to that of the present biomarkers: C-reactive protein and erythrocyte sedimentation rate. The 5 metabolites were significantly different among the patients and were valuable in the differentiation between CD and other chronic intestinal inflammatory diseases.
Conclusions: The combination of 5 serum metabolite biomarkers for the diagnosis of CD has the potential to provide an accurate, noninvasive, and inexpensive alternative to conventional tests and might be valuable for the differentiation from other diagnostically challenging intestinal inflammatory diseases.
Keywords: Behçet’s disease; Crohn’s disease; and intestinal tuberculosis; biomarker; metabolomics.
Serum metabolomic analysis was performed on patients with Crohn’s disease and healthy control subjects, which discovered 5 metabolites as a novel serum metabolomic panel. These metabolites were further validated in a second patient cohort and a third differentiation cohort. The data showed that these metabolites were valuable in diagnosis of Crohn’s disease and for differentiating it from other intestinal inflammatory diseases.
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