Clinical study on the screening of biomarkers for Crohn's disease based on blood metabolomics

Crohn's disease (CD) is a chronic inflammatory condition that affects the gastrointestinal tract. Currently, the diagnosis of CD is predominantly dependent on endoscopic procedures and histopathological tissue analysis. Endoscopy is an invasive procedure, patient compliance is poor, and the results are subject to the operator's subjective judgment. Infliximab (IFX) and ustekinumab (UST) are two new biologics used for the treatment of CD, which are effective in reducing inflammatory markers. However, the correlation between blood metabolites and inflammatory markers has rarely been studied in the biologic agents employed in the management of CD, and their effects on metabolic processes remain inadequately understood. This study aimed to elucidate the effects of IFX and UST on the blood metabolites in patients with CD, investigate the correlations between metabolic variations and clinical indicators, and examine the relationship between the identified biomarkers and clinical efficacy.

A total of 81 patients with CD who were receiving biologic therapy enrolled at week 16 between January 2022 and December 2023 (45 receiving IFX and 36 receiving UST) and 45 healthy controls were included. Metabolite profiling was performed using high-performance liquid chromatography-tandem mass spectrometry, followed by multivariate statistical and pathway enrichment analyses to identify differential metabolites and their correlations with clinical indicators.

Despite achieving clinical remission, both the IFX and UST groups exhibited significantly elevated C-reactive protein levels and erythrocyte sedimentation rate values compared with the control group (p < 0.05). IFX primarily influenced amino acid metabolism, including pathways involving arginine and glutamine, and glycolysis and the tricarboxylic acid cycle. UST impacted glutathione and purine metabolism. Pearson's correlation analysis demonstrated that l-arginine, l-glutamine, and l-lysine were significantly negatively correlated with C-reactive protein. In the UST group, glutathione, adenosine, and hypoxanthine were primarily significantly negatively correlated with C-reactive protein and absolute lymphocyte count (p < 0.05).

We identified two sets of diagnostic biomarkers: the biomarkers for the IFX group were l-arginine, l-glutamine, and l-lysine, while those for the UST group were glutathione and adenosine.