НАРУШЕНИЯ МИКРОБНОГО И ЭНДОГЕННОГО МЕТАБОЛИЗМА ПРИ ЯЗВЕННОМ КОЛИТЕ И ЦЕЛИАКИИ: МЕТАБОЛОМНЫЙ ПОДХОД К ВЫЯВЛЕНИЮ ПОТЕНЦИАЛЬНЫХ БИОМАРКЕРОВ ХРОНИЧЕСКОГО ВОСПАЛЕНИЯ В КИШЕЧНИКЕ, СВЯЗАННОГО С ДИСБИОЗОМ

Aim: to identify candidate biomarkers of ulcerative colitis and celiac disease by serum metabolomics analysis. Methods: 40 mild-to-moderate active left-sided UC patients, 43 CD patients in remission on a gluten-free diet and 42 healthy volunteers (HV) (125 patients in total) were enrolled in the study. Serum metabolomic assays were conducted using the GC-MS. Results: 28 out of 93 identified metabolites were of microbial origin. In serum of UC patients lactic acid, 2-hydroxybutyric acid (2-HBA), 3-hydroxyisobutyric acid (3-HIBA), 2-hydroxyisovaleric acid (2-HIVA), 3-hydroxycinnamic acid, succinic acid, benzoic acid and 4-hydroxyphenylacetic acid (4-HPAA) levels were significantly increased compared to HV. Serum levels of caproic acid, linoleic acid and eicosadienoic acid (EDA) in UC were significantly lower than in HV group. 2-HBA and 2-HIVA levels in UC patients were significantly increased as compared to CD patients. Serum levels of caproic acid, linoleic acid and glycolic acid in UC were significantly lower than in CD group. Serum of CD patients showed significant increases in stearic acid, 2-HIVA, succinic acid, fumaric acid and benzoic acid compared to HV. Serum arachidonic acid (AA) level in CD was significantly elevated compared to UC patients only. De novo lipogenesis index (DNL) (C16:0/C18:2n-6) was significantly elevated in UC patients compared to both HV and CD patients. The ELOVL6 elongase activity index (C18:0/C16:0) and the stearic acid/linoleic acid ratio (C18:0/C18:2n-6) in UC patients were significantly increased compared to HV. The ratio of AA to EDA (C20:4n-6/C20:2n-6) was increased in both UC and CD groups. Butyrate plus inulin significantly lowered serum levels of pro-inflammatory succinic acid (in both UC and CD patients) and 2-hydroxyisovaleric acid (in CD) and restored the lowered serum levels of linoleic acid and EDA in UC patients. Conclusions: Significant changes in serum levels of microbial and endogenous metabolites, reflecting some metabolic pathways disturbances (glycolysis, TCA cycle, fatty acid metabolism, ketone body metabolism, phenylalanine, tyrosine and tryptophan metabolism, microbial metabolism) are observed in both ulcerative colitis and celiac disease. ROC curve analysis showed that some of these metabolites of microbial or mixed origin, as well as a new metabolomic index (the ratio of arachidonic acid to eicosadienoic acid, C20:4n-6/C20:2n-6), reflecting the balance between pro-inflammatory and anti-inflammatory components of the omega-6 fatty acid pool, may be considered as candidate biomarkers of chronic intestinal inflammation. Reduction of pro-inflammatory microbial metabolites in serum indicates the ability of metabiotics (e. g. butyrate + inulin) to correct metabolic dysbiosis in both diseases.