Neverovskyi A. Cardiovascular risk correction by modification of gut bacterial bile salt hydrolase activity in patients with dyslipidemia

The results of dissertation propose to improve the treatment of dyslipidemia and correction of different categories of cardiovascular risk (CVR), evaluated using the validated scales, in patients with dyslipidemia based on the assessment and modification of the enzymatic activity of gut bacterial bile salts hydrolase (BSH) with BSH-producing probiotic strain of Lactobacillus plantarum. The topicality of the thesis is due to the significant contribution of disorders of lipid metabolism to the development and progression of atherosclerotic cardiovascular diseases (CVD) - the leading cause of morbidity and mortality from non-infectious factors in the world. The presence of side effects, high cost and limited access to existing therapeutic approaches in the treatment of dyslipidemia necessitate the investigation of new drugs that may have a hypolipidemic effect with possible further use in clinical practice to modify the CVR. The aim of the study. Improving the effectiveness of correction of non-fatal and fatal cardiovascular risks based on the assessment of the total activity of gut BSH and its modification in patients with dyslipidemia. Objectives of the study. 1. To assess the total activity of gut bacterial BSH in almost healthy individuals and in patients with dyslipidemia. 2. To assess the total activity of bacterial BSH of probiotics with BSH-producing strain of Lactobacillus plantarum. 3. To assess the total activity of gut bacterial BSH in the dynamic of treatment of the trial’s groups. 4. To evaluate the effect of probiotics with BSH-producing strain of Lactobacillus plantarum on the levels of lipid profile values. 5. Assess the impact of probiotics with BSH-producing strain of Lactobacillus plantarum on the levels of non-fatal and fatal CVR, assessed using validated scales. 6. Develop practical recommendations of the appointment of probiotics with BSH-producing strain of Lactobacillus plantarum for the correction of dyslipidemia and non-fatal and fatal CVR, assessed using validated scales. The dissertation research included 2 stages. The first stage was performed according to a case-control design, during which almost healthy participants and patients with dyslipidemia were selected, whose baseline parameters were determined, lipid profile values and total relative activity of gut bacterial BSH were measured, as well as different cardiovascular risk categories were evaluated using 5 validated scales. The second stage was designed as an open comparative randomized parallel study in which patients with dyslipidemia were divided into two comparison groups and treated with the study drugs for 12 weeks. During the second stage, at certain study time points (4, 8 and 12 weeks), patients of the compared groups were assessed on the lipid profile values, relative total activity of gut bacterial BSH and CVR levels using 5 validated scales.