According to the island biogeography theory, the heterogeneous composition of the microbiota in the human respiratory tract differs in density, diversity, structure, and composition between lower and upper airways. Understanding the fundamental process of the respiratory tract microbiota ontogenesis can help us to understand the function and the development of the lung in the context of health and disease, especially in patients with Cystic Fibrosis. This study included 210 samples of nasal swabs and 210 throat swabs from a cohort of 73 patients (infants and children) with CF, where 57 infants were followed up for at least two consecutive years. A 16s rDNA amplicon approach was applied to sequence all nasal and throat samples Illumina Miseq. The Alpha and Beta diversity analyses suggest community structure and composition stabilization over time in both sites but higher stability in the throat niches. An expectation-maximization analysis for microbial source tracking found more stable microbiota in the throat over age. The network analysis of the throat microbiome across sequential ages compared to the nose"s microbiome showed a significantly higher persistence of positive interactions between commensals despite the prevalence of pathogens. The goodness of fit of a drift-migration model used to predict the microbiota spatial progression in the upper respiratory tract suggests deterministic ontogenies after 1-year age, where the infant immune system was under development. Understanding the microbiota ontogenesis from the angle of the eco-evolutionary concepts can help in preventing the episodes of such respiratory disease exacerbation in the lungs of patients for instance with CF, using the microbiome dysbiosis patterns in the community structure and function as a diagnostic tool in a preventive manner to control the impact of the disease on the lower respiratory airways.