Background: Ulcerative colitis (UC) is an idiopathic and heterogeneous large intestine disease, characterized by chronic mucosa and submucosa inflammation. Alteration of the intestinal microbiome in UC may be responsible for modifications in metabolite production. Aim: To investigate the microbiota status and trimethylamine-N-oxide (TMAO) metabolite levels in patients with UC according to clinical and endoscopic activity. Methods: As part of a grant project AP14871959 from September 2022 to October 2023, 31 patients with UC and 15 healthy volunteers over 18 years at the Clinic of NCJSC “KMU” were assessed for blood TMAO level and metagenomic sequencing of fecal microbiome. Results: A significant depletion of the main representatives of Bacteroides, Parabacteroides, Prevotella; and an increase in the relative abundance of the genera Actinomyces, Klebsiella, Limosilactobacillus, Streptococcus, Escherichia-Shigella were detected in patients with UC. The number of p_Actinobacteria (g_Collinsella) and p_Eubacterium (g_Xylanophilum) representatives with genes encoding TMA-trimethylamine conversion is significantly reduced in UC patients. TMAO levels were significantly lower in UC patients than in healthy individuals (0.233 µmol/L, p = 0.004). TMAO decreased with disease severity and significantly differed between patients with different activities (p = 0.034). Conclusions: The composition of the intestinal microbiome changes and the level of TMAO decreases in patients with UC at different activities.

Background: The diagnosis of ulcerative colitis (UC) today is limited to a small number of biomarkers. Trimethylamine-N-oxide (TMAO) is the product of reactions resulting from the degradation of dietary-free choline, phosphatidylcholine, and carnitine metabolism by the intestinal microbiota. Earlier studies showed his involvement in the pathogenesis of UC. To study the association of TMAO with clinical, laboratory, and Methods: an observational cross-sectional comparative study was conducted based on the NCJSC "KMU" clinic, Karaganda, Kazakhstan. High-performance liquid chromatography measured TMAO concentration in 63 patients with UC (age Me 37 (30-52) and 38 healthy individuals (age Me 38 (28.5-49.5). Results: Median TMAO level in patients with UC-0.286 mu mol/l was significantly lower than in the control group Me 0.646 mu mol/l (p<0.0001). TMAO had significant differences in groups with clinically active and inactive colitis (P=0.003). TMAO correlated with disease activity by Montreal scale (r=-0.389, P=0.002) and severity of attack by Truelove-Witts (r=-0.301, P=0.027 respectively), patient's age (r=0.377, P=0.003), stool frequency (r=-0.427, P=0.001); laboratory parameters: WBC (r=-0.31, P=0.042), blood albumin (r=0.379, P=0.002) and fecal calprotectin (r=-0.314, P=0.022). TMAO did not differ between groups divided by the extent of the pathological process and endoscopic activity. Conclusion: in patients with UC, TMAO levels decrease compared with healthy individuals and differences in groups depend on the disease activity. These results give reason to consider changes in TMAO levels as a potential marker of UC and the severity of its course.

Crohn’s disease (CD) is a multifactorial inflammatory bowel disease whose pathogenetic mechanisms are a field of ongoing study. Changes in the intestinal microbiome in CD may influence metabolite production and reflect the disease’s severity. We investigate the relationship between trimethylamine N-oxide (TMAO) and lipopolysaccharide-binding protein (LPS) levels and changes in the gut microbiome in patients with CD of various degrees of activity. Methods: In total, 29 CD patients and 15 healthy individuals were investigated for their levels of TMAO by HPLC-MS, and LPS protein by ELISA and metagenomic 16 s-sequencing of feces was performed. Results: We found significant differences in TMAO levels in patients in the remission/mild and moderate/severe groups compared to the control group (p = 0.02 and p = 0.014), changes in alpha diversity with the Shannon index (p = 0. 0151 and p = 0.0018) and in beta diversity (ANOSIM p = 0.009 and PERMANOVA p = 0.005) in both groups compared to controls. Strongly positive correlations in TMAO levels and mixed correlations of LPS with alpha diversity metrics were found, as well as significant correlations with microbiota species. Conclusions: Changes in the level of metabolites may reflect specific disturbances in the composition of the intestinal microbiome at different degrees of severity of CD.