Proceedings of the International scientific and practical conference ―Synergy of Modern Science and Education‖ (June 12-14, 2026) / Publisher website: www.naukainfo.com. – New York, USA, 2026. - 145 p.

118 MEDICAL SCIENCES AND PUBLIC HEALTH UDC 612.67: 612.8]: 612.015.36+579.8 Rusalov Vitalii Leonidovych Lagodych Tetiana Sergiivna candidate of medical sciences, associate professor Lukianenko Iryna Anatoliivna candidate of biological sciences, associate professor Lazarеnko Viktoriia Oleksandrivna medical student (MD program) Bogomolets National Medical University Kyiv, Ukraine THE ROLE OF EARLY-LIFE MICROBIOTA PROGRAMMING AND AGE-RELATED NEUROENDOCRINE HOMEOSTASIS REMODELING IN THE MODULATION OF COGNITIVE AGING Abstract. The role of early-life microbiome programming and age-related neuroendocrine homeostasis remodeling in the development of cognitive aging is considered. Current data on the influence of the gut–brain axis, intestinal microbiota, neuroinflammation, insulin resistance, and hormonal changes on neuroplasticity, the functional state of the central nervous system, and the development of neurodegenerative processes are summarized. It is shown that early dysbiosis, impairment of the intestinal barrier function, chronic low-grade systemic inflammation, and age-related deficiency of neuroprotective hormones may represent important factors contributing to cognitive decline and the acceleration of neurodegenerative changes during aging. Keywords: gut microbiome, gut–brain axis, cognitive aging, neuroendocrine homeostasis, neuroinflammation, hypothalamic–pituitary–adrenal axis, neurodegeneration, insulin resistance, neuroplasticity. The concept of early-life microbiota programming suggests that the pattern of primary intestinal colonization in infants under the influence of breastfeeding determines the architectonics and maturation of synapses in the central nervous system through the gut–brain axis [1, 2]. The microbiome is considered a complex metabolically active system capable of modulating immune, endocrine, and neural regulation. Of particular interest is the concept of the gut–brain axis, which describes the bidirectional interaction between the central nervous system and the intestinal microbiota through neural, humoral, and immune mechanisms [3, 4]. A key role in the modulation of cognitive status is played by bacterial metabolites, including short- chain fatty acids, tryptophan derivatives, bile acids, neurotransmitter-like compounds, and antioxidant polyphenol metabolites, which influence neuroinflammation, neuroplasticity, barrier functions, and brain energy metabolism. Age-related changes in the intestinal microbiota, accompanied by reduced microbial diversity and the development of chronic low-grade inflammation (inflammaging), may represent one of the pathogenetic factors contributing to cognitive decline in older individuals [2]. The composition of the microbiome in early life modulates the expression of genes responsible for the stress resilience of the hypothalamic–pituitary–adrenal (HPA) axis, thereby protecting the brain from premature aging. Alterations in the microbiome composition during early life, particularly due to antibiotic therapy, formula feeding, infections, or chronic stress, may affect HPA axis activity and increase cortisol secretion in response to stress stimuli. This is accompanied by changes in neurotransmitter metabolism, neuroinflammation, and impaired expression of genes associated with stress resistance and neuroplasticity, including brain-derived neurotrophic factor (BDNF). As a result, the risk of anxiety, depressive, and stress- related disorders later in life increases [5]. In addition, early dysbiosis may have long-term consequences for brain functional status, since alterations in the interaction between the microbiota and the HPA axis can influence cognitive functions,