Meleshko T. Intestinal microbiota in common non-communicable human diseases and its personalized correction in the treatment of patients with type 2 diabetes

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0421U102364

Applicant for

Specialization

  • 03.00.07 - Мікробіологія

12-05-2021

Specialized Academic Board

Д 64.618.01

State Institution "I. Mechnikov Institute of Microbiology and Immunology National Academy of Medical Sciences of Ukraine"

Essay

The object of research: features of the intestinal and oral microbiota associated with noncommunicable diseases (NCDs) (atherosclerosis, obesity, type 2 diabetes mellitus (T2D) and cardiovascular disease (CVD)). The purpose of research: to find out typical for common NCD individual ratios of functional groups of human intestinal microbiota, biochemical and immune parameters and to realize the possibility of experimental verification of the NCD treatment idea by application of microbiota targeted correction through the personalized diet plans. Research methods: microbiological (examination of oral and intestinal microbiota composition, counting the number of viable cells, isolation of pure cultures of microorganisms and their species identification); microscopic (determination of morphological and tinctorial properties of bacteria); physico-chemical: spectrophotometric method (determination of the total content of biologically active substances (BAS)); biochemical (determination of biochemical parameters of patients' serum); molecular genetic (quantitative determination of microorganisms using real-time polymerase chain reaction); immunological (determination of immune parameters of patients with T2D using solid-phase enzyme-linked immunosorbent assay (ELISA)); statistical (processing of the obtained research results, prioritization of biomarkers for T2D was performed using the correlation analysis of experimental data, principal component analysis, factor and cluster analysis). Equipment: DeNovix DS-11 FX + spectrophotometer / fluorimeter (DeNovix Inc., USA); real-time PCR system AriaMX (Agilent Technologies, USA); automatic hematology analyzer Mythic 22 (Orphee S.A., Switzerland) and Cobas c 311 (Roche / Hitachi, Switzerland); IW-8 automatic plate washer (BioSan, Latvia); BioTek Elx800 plate immunoassay analyzer (BioTek Instruments Inc., USA); KFK-3 spectrophotometer (Russia). The dissertation is devoted to the definition of typical for the studied region features of the main functional groups of intestinal microbiota ratios of persons with atherosclerosis, obesity, T2D and CVD, as well as conformation of the effectiveness of microbiota targeted correction through the personalized diet plans. Individual and nosologically specific ratios of functional groups of representatives of intestinal microbiota of persons with atherosclerosis, obesity, CVD and T2D have been established. Personalized nutrition plans have been created, which include individually selected probiotics and plant foods with prebiotic properties, which together provide a targeted effect on the intestinal microbiota. The efficacy and effectiveness of targeted correction of the gut microbiota by means of a personalized nutrition plan in the treatment of patients with T2D has been clinically confirmed. Adherence to the proposed diet led to the normalization of intestinal and oral microbiota, a decrease in blood glucose, thymol test, VLDL, creatinine, urea, SIgA and TNF-α, increased levels of uric acid, sodium, magnesium, as well as a decrease in the values of the following physical parameters: body weight, waist circumference, thigh girth, upper thigh girth and BMI. The main correlations between the change of certain functional groups of the intestinal microbiota, immune parameters and biochemical parameters are revealed. An orderly list of microbial, biochemical and immune markers of the process of personalized treatment of T2D by correcting the intestinal microbiota have been obtained. The most representative markers proved to be the following: E. faecalis (saliva), TNF-α, creatinine, urea, thymol test, Na, Lactobacillus spp. (saliva), E. faecalis (stool), E. coli (lac -) (stool), Lactobacillus spp. (stool). Theoretical generalization and solution of scientific and practical problem is the possibility of using the typical rations of the main functional groups of the intestinal microbiota as new multicomponent microbial markers of atherosclerosis, obesity, T2D and CVD. Clinical confirmation of the effectiveness of targeted correction of the microbiota with the help of personalized food justifies and demonstrates the possibility of practical use of a new approach to the prevention and treatment of NCDs. The method of prioritization of biomarkers used in the work has a practical use as part of a new method of "feature selection" - the optimal selection of data for machine learning. The extent of implementation: 6 acts of implementation. The field (industry) of use: healthcare (medicine: microbiology, immunology, non-communicative diseases).

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