SCIENTIFIC FOUNDATIONS AND HISTORICAL EVOLUTION OF THE HUMAN MICROBIOTA: FROM THE HUMAN GENOME PROJECT TO THE HUMAN MICROBIOME PROJECT

The 21st century has accelerated all aspects of biological research; however, one of the areas where this effect has been most striking is in studies on microbial communities and the human microbiome. In the 22 years since the first human genome was published, microbiome studies have expanded from culture-based research in areas such as the mouth and gut to molecular profiles of microbial biochemistry in all ecological niches of the human body. The long evolutionary process between the human host and the gut microbial community (gut microbiota) has created a close interaction between them; the microbiota is 10 times more abundant than the somatic and reproductive cells of the human body and 100 times more abundant than human genes. This situation demonstrates that human biology cannot be reduced to its own genome alone, and that microbial functional diversity is a fundamental component of physiological homeostasis and immune regulation. The inadequacy of the genetic determinism paradigm in explaining biological complexity after the Human Genome Project (1990–2003) accelerated the rise of systems biology and metagenomic approaches. Launched within this framework, the Human Microbiome Project (HMP, 2007) defined the microbial communities in the human body in terms of their taxonomic and functional aspects, addressing health in the context of “microbial ecosystem balance.” The subsequent EU-funded MetaHIT project (2008) revealed that the gut microbiome contains approximately 3.3 million distinct microbial genes, bringing the metabolic capacity of the gut ecosystem to the forefront of the scientific agenda. The subsequent Integrative Human Microbiome Project (iHMP, 2014–2019) integrated metagenomic data with metatranscriptomic, metabolomic, and proteomic analyses to examine the metabolic, immunological, and epigenetic consequences of host–microbiota interactions within a dynamic network model. This approach positioned dysbiosis as a common etiological component of many complex diseases and laid the foundation for the development of new therapeutic strategies such as fecal microbiota transplantation and targeted microbiota modulation. Consequently, a new scientific paradigm has emerged in which the genome-centered biological understanding has been replaced by the concept of “holobiont”; humans are defined not merely as organisms, but as multilayered metagenomic superorganisms. This transformation indicates that microbial ecosystems will be considered an indispensable component for sustainable health in the future of molecular biology.