Study of the association of trimethylamine N-oxide and lipopolysaccharidebinding protein levels with the activity of inflam

AP14871959

Objective:The goal of the project is to study the concentrations of trimethylamine Noxide and lipopolysaccharide-binding protein in the blood of patients with inflammatory bowel diseases and assess their relationship with disruption of the intestinal microbiota and disease activity.

Relevance.

The study of IBD markers is a priority, since, according to epidemiological data, the prevalence of ulcerative colitis and Crohn's disease in the world ranges from 4 to 20 cases per 100 thousand population, depending on different regions of residence, and the annual increase in incidence according to the global trend is 5 —20 cases per 100 thousand population.An important aspect is that untimely diagnosis of the disease leads to a more severe course, widespread damage, an increase in the number of surgical interventions and early disability of patients, especially among the young, working population. Characteristics of the course of IBD are based on a combination of clinical, histological and endoscopic data.The main method of diagnosis is undoubtedly endoscopic evaluation with histological examination, but biomarkers from blood and stool samples are used to monitor disease activity. White blood cell counts, Creactive protein (CRP), and fecal calprotectin can help distinguish IBD from noninflammatory diarrhea and assess disease activity. But being “non-specific”, CRP and leukocytes do not always help in diagnosing IBD.As for fecal calprotectin, the literature suggests that despite its high sensitivity and specificity, it is a reliable marker, but its ability to assess in ulcerative colitis is higher than in Crohn's disease. The widespread use of metagenomics is currently giving great impetus to the study of the role of various metabolites of the gut microbiome in the pathogenesis of diseases. In particular, it is trimethylamine-N-oxide, as well as a marker of leaky gut syndrome, lipopolysaccharide-binding protein.Both of them are involved in the process of stimulation of the NLRP3 inflammasome, which in turn triggers the overproduction of proinflammatory cytokines, increasing chronic inflammation, and hence the course of IBD.

Expected results:

Clinical, laboratory, endoscopic and histological characteristics of patients with IBD of varying degrees of activity will be given, features of the microbial landscape will be determined, the concentration of TMAO and LPS protein will be determined and it will be established whether the altered level of TMAO and LPS protein reflects disturbances in the composition of the intestinal microbiota and activity of the pathological process in IBD.

    Research group:
  1. Laryushina E.M. - scientific supervisor of the project, candidate of Medical Sciences, Professor, Head of the Department of Internal Diseases of NJSC "Medical University of Karaganda" Hirsch index 4, author's identifier in Scopus: 57196123971, ORCID 0000-0002-9590-690X.
  2. Turgunov E.M. - senior Research Fellow, doctor of Medical Sciences, Professor, Vice-Rector for Scientific and Clinical Work of NJSC "Medical University of Karaganda". H-index 2, Scopus author ID: 57193721109, ResearcherID: R-2915-2016, ORCID: 0000-0002-6486-3847
  3. Marchenko A.B. - senior Researcher, PhD, Leading Researcher, SL NJSC "Medical University of Karaganda" Hirsch index 2, Scopus author ID: 57193758669, ORCID 0000-0002-0325-7659.
  4. Samoilova N.M. - junior researcher, PhD doctoral student of the 2nd year of study in the specialty 8D10100 "Medicine", gastroenterologist, assistant of the Department of Internal Diseases of NJSC "Medical University of Karaganda". ORCID: 0000-0003-0461-7078
  5. Shkreba A.P. - junior researcher, resident of the 2nd year of study in the specialty "General Surgery", endoscopist.
  6. Zhumadilova Zh,A. - junior Research Fellow:, Master of Science, Research Fellow, SL NJSC "Medical University of Karaganda". ORCID: 0000-0003-3227-1692.
  7. Seisenbekova A.K. - junior researcher, gastroenterologist, assistant of the Department of Internal Diseases of NJSC "Medical University of Karaganda".

The degree of achievement of set goals and objectives is high. The tasks are carried out strictly according to plan and comply with the technical specifications of the contract.

The results of the examination (clinical, laboratory studies, data from endoscopic, morphological, radiological examination methods) of 50 study participants (40 patients with IBD, 10 respondents in the control group) included in the study for 2022 were entered into the database.

84 (69 with IBD, 15 control group respondents) study participants, after a preliminary telephone conversation, were invited to the medical university clinic, a clinical examination of 84 patients with IBD was carried out, including: collection of complaints, data on the medical history and life, physical examination of the patient, analysis of the results of previous laboratory, instrumental examinations, hospitalizations, treatment plans, examination results (clinical, laboratory studies, data from endoscopic, morphological, radiation examination methods),entered into the database, biological materials were collected, the level of TMAO in the blood serum and LPS protein was determined, the results of a general blood test, the level of total protein, albumin, CRP in the blood serum, fecal calprotectin were obtained at the National Laboratory Astana Private Institution. stool samples were delivered

Statistical processing of the research results using the IBM SPSS Statistics 22 program has begun.

3 employees of VNK received membership in the international organization ECCO in 2023 (European Society for the Study of Crohn's Disease and Ulcerative Colitis): Laryushina E.M., Samoilova-Bedych N.M., Seisenbekova A.K

. The results of the research were presented in the form of reports at conferences.

Being fundamental in nature, the study will answer the questions posed and decide whether there is a need for further work in this direction, whether it is promising, and whether alternative methods of correcting the condition are possible for patients with IBD.This will make it possible not only to theoretically approach the choice of diagnostic and treatment strategies, but also to expand the capabilities of the clinician, which will subsequently lead to earlier diagnosis, and therefore more productive and effective treatment of patients

Information for potential users

researchers, GPs, gastroenterologists, resuscitators, general practitioners, patients with IBD..

Dissemination of work results: publications in foreign and domestic publications, implementation in the educational process when teaching theoretical and clinical disciplines.

Main publications on the project topic
  1. Prevalence and risk factors of IBD (according to the register of the Karaganda region), Zhirenbaeva A.M., Igenbekova A.T., VIth Central Asian International Scientific and Practical Conference on Medical Education “Education of the Future: Wind of Change”, Karaganda, NAO MUK , Karaganda, 20-21.04.23 (poster report);
  2. Epidemiological assessment and factors of inflammatory bowel diseases in patients of Central Kazakhstan, Samoilova-Bedych N.M., 25th International Medical Slavic-Baltic International Forum “St. Petersburg-Gastro-2023-ON-Line”, May 18, 2023 ( oral report);
  3. New facets of studying intestinal metabolites: TMAO and IBD. Laryushina E.M., SamoilovaBedych N.M., Republican conference with international participation dedicated to “World Digestive Health Day”, Astana, June 2, 2023 (oral report)
  4. TMAO (trimethylamine N-oxide): a metabolite as a biomarker for inflammatory bowel disease? Samoilova-Bedych N.M., Laryushina E.M., Seisenbekova A.K., Marchenko A.B., Igenbekova A.T., Zhirenbaeva A.M. TWENTY-NINTH UNITED RUSSIAN GASTROENTEROLOGY WEEK, Moscow, RF, September 26-28, 2023 (oral report, publication of thesis);
  5. TRIMETHYLAMINE-N-OXIDE AND ACTIVITY OF INFLAMMATORY BOWEL DISEASES, N.M. Samoilova-Bedych, E.M. Laryushina, N.V. Kabdulina, A.M. Zhirenbaeva, VIII Central Asian Gastroenterological Week, Almaty, October 5-7, 2.23 (poster presentation)
  6. Accepted for publication and approved oral presentation: Trimethylamine N-oxide: a metabolite associated with Crohn's disease? Samoilova-Bedych N.M., Laryushina Y.M., Marchenko A.B., Seisenbekova A.K., Bangkok, Thailand, Asian Pacific Digestive Week, December 6-9, 2023.