Over the last decade, scientific understanding of the human body has shifted from an anthropocentric model to the concept of the holobiont – an integrated ecological unit consisting of the host and its microbiome. The interaction between the human genome and microbiota is a key determinant of physiology, metabolism, and disease susceptibility, yet the mechanisms of this genetic control remain insufficiently systematized.

Aim. To analyze current data on the influence of the host genome on the formation and control of gut microbiota composition and function, and to identify key genetic loci and molecular mechanisms of interaction within the “genome – microbiome” system.

Materials and methods. A review of scientific literature was conducted using PubMed, Scopus, and Web of Science databases. Results from genome-wide association studies (GWAS), twin studies, and molecular genetic research were analyzed.

Results. Host genetics represents a significant factor in shaping the microbial profile, with heritability estimates for specific taxa ranging 5–45 %. Two main mechanisms of genetic control are identified: immune sculpting (genes NOD2, IL23R) and metabolic gardening (genes LCT, FUT2, APOA5). Synergistic effects of defects in these systems significantly increase the risk of chronic inflammatory and metabolic diseases. The hologenome concept, which views the combined genome of the host and microbiome as a single unit of evolution, is described.

Conclusions. The host genome actively shapes the microbial ecosystem through immunological and metabolic mechanisms. Understanding these interactions paves the way for personalized medicine based on a hologenomic approach, particularly for developing individualized microbiome correction strategies.