GUT MICROBIOTA AND ITS ROLE IN THE DEVELOPMENT OF ENDOCRINE DISEASES: ENDOCRINE AND PHARMACOLOGICAL ASPECTS

Abstract

Gut microbiota (GM) is increasingly recognized as an integral component of endocrine regulation, contributing to the maintenance of hormonal and metabolic homeostasis. The microbial community of the gastrointestinal tract functions as a metabolically active system capable of producing a wide range of bioactive compounds, including short-chain fatty acids, secondary bile acids, and other signalling molecules with hormone-like activity. These compounds interact with receptor systems in target cells and modulate endocrine signalling pathways. In preparing this paper, we performed a systematic analysis of contemporary scientific publications indexed in international scientometric databases, which allowed us to synthesize current experimental and clinical evidence on the role of gut microbiota in the pathogenesis of endocrine diseases. Dysbiosis is associated with the development of insulin resistance, impaired incretin responses, chronic low-grade systemic inflammation, and metabolic endotoxemia, which are key pathogenetic links in type 2 diabetes mellitus (T2DM) and obesity. We discuss the impact of microbiota on the endocrine function of adipose tissue, leptin and adiponectin secretion, and appetite regulation via the gut-brain axis. We analyze GM involvement in the hypothalamic-pituitary-adrenal (HPA) axis, its influence on cortisol secretion, and organismal adaptive responses to stress. The role of microbiota in thyroid hormone metabolism, immune tolerance, and the development of autoimmune thyroid diseases is highlighted within the concept of the gut-thyroid axis. Particular attention is paid to interactions between the microbiota and sex hormones, and to their relevance to polycystic ovary syndrome and reproductive endocrine disorders. We also consider GM's capacity to modify the pharmacokinetics and pharmacodynamics of endocrine medications, thereby influencing interindividual variability in therapeutic response. The potential of microbiota-oriented adjunct strategies as a tool for personalizing endocrine pharmacotherapy and optimizing the prevention and treatment of endocrine diseases is emphasized.

The aim of the review: to summarize current experimental and clinical data on the role of the intestinal microbiota as an integral component of endocrine regulation, to determine its importance in the formation of hormonal and metabolic homeostasis, to reveal the mechanisms of dysbiosis in the pathogenesis of major endocrine diseases (T2DM, obesity, thyroid and reproductive pathology) based on a systematic analysis of modern scientific publications indexed in international scientometric databases Scopus, Web of Science Core Collection, PubMed/MEDLINE, Embase, Google Scholar, etc., and to substantiate the prospects of microbiota-oriented approaches in the personalization of endocrine pharmacotherapy.