The aim of the work was to study the peculiarities of the effect of glucagon-like peptide-1 receptor agonists on the metabolic activity of the intestinal microbiome depending on the morpho-phenotypic characteristics of patients with type 2 diabetes. The results of the examination of 153 patients with type 2 diabetes aged from 31 to 75 years were analyzed, the average level of HbA1c was 7.83±1.55% against the background of previous treatment. Anthropometric parameters, body mass index (BMI), body composition (bioelectrical impedance method), characteristics of carbohydrate and lipid metabolism, levels of GLP-1 and microbial metabolites (SCFAs and TMAO), serum concentration of the oxidative stress marker 8-iso-PGF2α were measured. Discussion and conclusions. After ranking according to the value of BMI, patients were divided into 4 groups, between which the levels of 8-iso-PGF2α and SCFAs were compared. It was established that simultaneously with an increase in BMI, percentage of fat content, level of visceral fat, an increase in the concentration of 8-iso-PGF2α was observed (p<0.05). Inverse correlations were found between BMI values and levels of triglycerides in the coprofiltrate (p<0.05), that is, a relationship was found between the signs of the obesity phenotype, the degree of oxidative stress in the body of patients with type 2 diabetes and the functional activity of intestinal bacteria, namely the synthesis SCFAs. When investigating the relationships between phenotypic morphological features, the function of the intestinal microbiota, assessed by the level of SCFAs, and the indicators of tests for assessing the psycho-emotional state using questionnaires (n=101), a reliable direct correlation of the scores for assessing the hormonal imbalance of cortisol with the levels of total and visceral fat was noted, which in turn showed a reliable correlation with scores on the scale of anxiety and depression, distress in diabetes. These data indicate the feasibility of using these tests to assess the degree of psychological distress in patients with different phenotypes. It was established that after treatment with liraglutide in the maximum dose (n=88), there was an improvement in glycemic control and lipidemia, improvement in body composition (decrease in % of total and visceral fat, increase in SVI, body hydration). These changes were accompanied by a significant increase in the concentration of SCFAs in the coprofiltrate, which may indicate an improvement in the function/composition of the intestinal microbiota, namely SCFAs-producing bacteria. Against the background of the use of liraglutide (n=44), an increase in the level of endogenous GLP-1 in the blood was found (p<0.05), which may also be associated with a change in the composition of the intestinal microbiota. A significant decrease in the level of the proatherogenic and prothrombotic metabolite TMAO (n=44) in blood serum was revealed. The effectiveness of the use of arGLP-1 in patients with type 2 diabetes as a means of counteracting the development of neuropsychological disorders, taking into account the functional activity of the intestinal microbiota, was investigated. When assessing psychometric characteristics (degree of anxiety and depression, assessment of distress, coping with stress) with the help of a questionnaire, it was found that the characteristics of the psycho-emotional state of patients of both sexes improved: the general indicators according to the hospital scale of anxiety and depression, the total level of distress in diabetes, as well as points decreased according to the cortisol hormonal imbalance assessment scale (р<0.05). The detected changes were mostly observed in the group of women, in contrast to men, which indicates a particularly favorable effect of the applied therapy on the neuropsychological status of the patients, possibly in connection with the reduction of the influence of stress hormones. A direct correlation between the levels of SCFAs and psychometric data was noted. The results substantiate the expediency of the use of arGLP-1 therapy and prove their effectiveness in terms of influencing the metabolic activity of the intestinal microbiota, in particular, a decrease in the concentration in the blood serum of patients of the proatherogenic and prothrombotic metabolite TMAO, which will help reduce cardio-metabolic risk, and also arGLP-1 therapy contributed to an increase in the content in the coprofiltrate of short-chain fatty acids: acetate, propionate, butyrate, which will have a positive effect on the secretion of endogenous incretins. Key words: type 2 diabetes, obesity, metabolic syndrome, anthropometric and compositional indicators, carbohydrate and lipid metabolism, glucagon-like peptide-1, intestinal microbiota metabolites, trimethylamine-N-oxide, short-chain fatty acids, oxidative stress, 8 isoprostaglandin F2α, psychoemotional disorders, agonists of GLP-1 receptors, the size of the clinical effect.
