Молодежный инновационный вестник

2415-7805

Федеральное государственное бюджетное образовательное учреждение высшего образования "Воронежский государственный медицинский университет имени Н.Н. Бурденко" Министерства здравоохранения Российской Федерации

11221

Conference Proceedings

The role of human microbiota in the development of atherosclerosis and thrombosis

Gmirya

Anastasia Alexandrovna

nastiagmirya03072003@list.ruhttps://orcid.org/0009-0007-4286-6901Shvechikova

Valeria Alexandrovna

ValeriShvechikova@yandex.ruhttps://orcid.org/0009-0004-0221-5598

M. Gorky Donetsk State Medical University

01102026

15S19092

24022026

10032026

2026

According to studies conducted in 2020-2025, the intestinal microbiota plays a role in the development of various cardiovascular diseases. The intestinal microbiota functions as an endocrine organ. It has been proven that an imbalance in the taxonomic composition of the microbiota leads to various metabolic disorders in lipid and carbohydrate metabolism. The purpose of this study is to summarize the current literature on the role of intestinal bacteria in the progression of atherosclerosis and thrombosis, as well as to describe the mechanisms underlying the pathogenesis of these diseases. Materials and methods. We have analyzed domestic and foreign articles, abstracts of candidate and doctoral dissertations on the research topic. Results. In the course of literature analysis, we have identified several key functions of intestinal bacteria that contribute to the development of atherosclerosis and thrombosis: synthesis of secondary bile acids, regulation of the synthesis of secondary bile acids by negative feedback, synthesis of TMA (trimethylamine), PAG (phenylacetylglutamine), TMAO (trimethylaminoxide). A provoking factor for the synthesis of TMAO and TMA is a high consumption of dairy products and red meat (they contain such compounds as lecithin, choline, L-carnitine TMA precursors). TMAO changes the concentration of Ca2+ ions inside platelets, triggers the activation of integrin glycoprotein IIb/IIIa, which in turn accelerates the processes of platelet adhesion. Conclusion. Atherosclerosis and thrombosis are inextricably linked to the gut microbiota. Intestinal dysbiosis leads to the progression of these pathologies.

intestinal microbiotaatherosclerosisTMATMAOPAGmetabolitesCYP7A1

микробиота кишечникаатеросклерозТМАТМАОPAGметаболитыCYP7A1

Introduction. The intestinal microbiota comprises over a trillion microorganisms. Metabolites of intestinal bacteria, such as TMAO and secondary bile acids, influence a large number of metabolic processes in the human body, contributing to the progression of atherosclerosis and thrombosis. This opens a new direction in cardiology aimed at correcting the microbial profile to reduce cardiovascular risk. Objective. To collect relevant data on the role of intestinal dysbiosis in the development of cardiovascular risk factors that contribute to the development of atherosclerosis; the mechanisms are considered in detail: synthesis of TMA, synthesis of secondary bile acids, synthesis of PAG by microbiota. Materials and methods. An analysis of materials from domestic and international medical research databases (Pubmed, elibrary.ru) was conducted. Results. The intestinal microbiota is a heterogeneous collection of microorganisms (viruses, bacteria, some types of fungi) that inhabit the gastrointestinal tract. A significant part of the microbiota is represented by bacteria: Firmicutes - 64%, Bacteroides - 3%, Verrucomicrobes - 2%, Proteobacteria - 2%, etc. Traditionally, several functions of intestinal bacteria are distinguished: 1) synthesis of secondary bile acids (BA); 2) synthesis of TMA (trimethylamine); 3) synthesis of PAG (phenylacetylglutamine). Secondary bile acids (deoxycholic and lithocholic acid) are synthesized from primary bile acids under the action of intestinal microbiota enzymes. The synthesis of primary bile acids is regulated by negative feedback. The farnesoid X receptor (FXR) plays a key role in this process. When activated by ligands (secondary bile acids) of intestinal FXR, fibroblast growth factor (FGF19) is expressed. FGF19, by binding to a receptor on the hepatocyte membrane, inhibits the synthesis of bile acids by suppressing the activity of cholesterol-7-alpha-hydroxylase (CYP7A1), a rate-limiting enzyme. Direct activation of liver FXR also inhibits the conversion of cholesterol to bile acids. Activation of this pathway also slows down lipogenesis in the liver and stimulates -oxidation of fatty acids in the liver mitochondria. Bacteroides taiotaomicron is capable of accelerating lipid hydrolysis by increasing the production of colipase [1]. When negative feedback is disrupted, the process of fat emulsification is disrupted, which can lead to steatorrhea, a deficiency of fat-soluble acids, disruption of cholesterol homeostasis and, consequently, the progression of atherosclerosis (Fig. 1). TMAO (trimethylamine-N-oxide) is a compound, high levels of which are directly associated with an increased risk of cardiovascular disease. The precursor of TMAO is TMA, which in turn is synthesized from compounds such as lecithin, choline, L-carnitine. These compounds are found mainly in food of animal origin (for example, in red meat, dairy products, etc.). Lecithin and choline are metabolized by the intestinal microbiota to form Figure 1. Diagram of the relationship between the intestinal microbiota and the cardiovascular system 1 - intestinal wall; 2 - portal vein; 3 - liver; 4 - platelets; 5 - heart; 6 - vessel wall in atherosclerosis; 7 - vessel wall in thrombosis; 8 - intestinal bacteria TMA and TMA gas are catalyzed by the enzyme choline-TMA lyase. TMA is then transported via the portal vein to the liver, where FMO (flavin monooxygenase) oxidizes TMA to TMAO. Changes in the TMAO/TMA ratio also affect thrombus formation [2]. TMAO has been shown to alter platelet calcium signaling. High intraplatelet Ca2+ concentrations trigger activation of integrin glycoprotein IIb/IIIa; secretion of granules containing serotonin and ADP (adenosine diphosphoric acid); and exposure to phosphatidylserine, which in turn accelerates platelet adhesion and thrombin formation, especially when stimulated by collagen. TMAO also induces expression of tissue factor in endothelial cells, one of the initiators of the extrinsic coagulation pathway. TMAO can also cause inflammation in the vascular wall. Thus, studies have confirmed that even after TMAO was removed from the bloodstream, vascular adhesion molecules (E-selectin, ICAM-1) continued to be expressed. This process is apparently facilitated by oxidative stress, which is mediated by NLRP3 inflammasomes in endothelial cells, increased production of reactive oxygen species (ROS), and destabilization of endothelial cell lysosomes. In turn, reactive oxygen species oxidize low-density lipoproteins (LDL) into oxidized low-density lipoproteins (ODL). ODL is the basis for the formation of foam cells, one of the key cells in atherosclerotic plaques [3]. Phenylalanine is an essential amino acid. The intestinal microbiota also participates in its metabolism. The conversion of phenylalanine to phenylacetylglutamine (PAG) occurs through several sequential reactions under the action of microbiota enzymes: phenylalanine phenylpyruvic acid phenylacetic acid. In the liver, phenylacetic acid undergoes N-acetylation with glutamine to form PAG. PAG then interacts with - and -adrenergic receptors on platelets, which, via the G protein, implements its effects, namely, thrombus formation [4]. Thus, these studies helped to explain some of the beneficial effects of -blockers (in particular, carvedilol) in the treatment of patients with atherosclerosis. It is known that the final stage of many cardiovascular diseases, including atherosclerosis, is heart failure (HF). There is increasing evidence that a decrease in ventricular heart rate can lead to edema and ischemia of the intestinal mucosa. These pathophysiological processes can alter the bacterial composition of the intestinal microbiota, increase the permeability of the intestinal wall, which ultimately leads to the release of endotoxins into the bloodstream and the development of chronic inflammation. Certain bacterial strains (Candida, Campylobacter, Shigella) significantly increased intestinal permeability [5]. Studies have found a correlation between peripheral edema in patients with heart failure, inflammatory cytokines and the level of bacterial endotoxins in the blood [4]. It is noteworthy that therapy with potassium-sparing diuretics significantly reduced the amount of circulating bacterial endotoxins in the blood, especially in patients with chronic heart failure (CHF). Conclusion. Various changes in the metabolic processes of the microbiota lead to the progression of cardiovascular diseases. The identified "gut cardiovascular disease" relationship creates a scientific basis for the targeted use of pre- and probiotics not only to correct dysbacteriosis, but also to improve the functioning of the cardiovascular system.

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