Метаболомный профиль сыворотки крови у пациентов с язвенным колитом: патофизиологическая роль, диагностическое и терапевтическое значение

Abstract

The incidence of inflammatory bowel disease (IBD) in both children and adults is increasing worldwide. While Crohn’s disease predominates in the pediatric population, ulcerative colitis (UC) more often affects the elderly. The relevance of metabolomic profiling in IBD has been confirmed in several studies revealing changes in endogenous and microbial metabolism associated with their pathogenesis. The metabolome composition of body fluids depends significantly on sex since sexual dimorphism is a trigger for metabolic differences between organisms. We have previously studied serum metabolic profiles in male patients with UC and identified candidate biomarkers of the disease. Objective. To determine the features of metabolome composition and candidate metabolite biomarkers of UC in women using a non-targeted serum metabolomic analysis. Patients and methods. This study included 10 women with active UC (moderately severe and severe attacks; a study group) aged 23 to 61 years (mean age: 35.2 ± 13.5 years) and 10 age-matched healthy volunteers (a control group) without IBD. Serum metabolites were analyzed by gas chromatography-mass spectrometry. Sample classification and search for potential biomarkers were performed using a partial least squares-discriminant analysis (PLS-DA), support vector machines (SVM), and a naïve Bayes classifier. ROC curves and areas under correlated curves were used to compare the success of different methods. Results. In serum samples from patients with UC and healthy volunteers, up to 90 low molecular weight compounds with different mass spectra and retention times were identified. The analysis revealed 25 compounds whose concentrations in the blood differed significantly between the study group and the comparison group (p <0.05). Six of the 25 compounds (adipic acid, β-glycerophosphate, glyceric acid, 2-hydroxybutyric acid, squalene, 2-palmitoylglycerol) were among the most significant 15 compounds detected by two classifiers at once (PLS-DA and SVM). Of these 15 compounds, only 7 were identical to the compounds that significantly altered in men: 2-hydroxybutyric acid, creatinine, β-glycerophosphate, α-glycerophosphate, trans-palmitoleic acid, palmitic acid, and squalene. Some of these compounds, just as in men, were associated with lipid metabolism disorders and glycolysis regulation (α-glycerophosphate), as well as with impaired osteogenesis (β-glycerophosphate). Conclusion. Significant differences were found between serum metabolomic profiles in women with UC and healthy volunteers. About half of the most significant compounds detected in the study group were identical to the compounds that were significantly altered in men with UC. In future investigations, the results obtained by non-targeted metabolomics, as well as the exact mechanisms of metabolic changes in UC patients, should be confirmed and clarified using targeted metabolomics and other omics. Key words: inflammatory bowel disease, ulcerative colitis, metabolome, biomarkers, gas chromatography-mass spectrometry