Early-life nasal microbiota dynamics relate to longitudinal respiratory phenotypes in urban children

Background: Five distinct respiratory phenotypes based on latent classes of longitudinal patterns of wheezing, allergic sensitization. and pulmonary function measured in urban children from ages from 0 to 7 years have previously been described. Objective: Our aim was to determine whether distinct respiratory phenotypes are associated with early -life upper respiratory microbiota development and environmental microbial exposures. Methods: Microbiota profiling was performed using 16S ribosomal RNA-based sequencing of nasal samples collected at age 12 months (n = 120) or age 36 months (n = 142) and paired house dust samples collected at 3 months (12 -month, n = 73; 36 -month, n = 90) from all 4 centers in the Urban Environment and Childhood Asthma (URECA) cohort. Results: In these high -risk urban children, nasal microbiota increased in diversity between ages 12 and 36 months (ss = 2.04; P = .006). Age -related changes in microbiota evenness differed significantly by respiratory phenotypes (interaction P = .0007), increasing most in the transient wheeze group. At age 12 months, respiratory illness ( R 2 = 0.055; P = .0001) and dominant bacterial genus ( R 2 = 0.59; P = .0001) explained variance in nasal microbiota composition, and enrichment of Moraxella and Haemophilus members was associated with both transient and high -wheeze respiratory phenotypes. By age 36 months, nasal microbiota was significantly associated with respiratory phenotypes ( R 2 = 0.019; P = .0376), and Moraxella - dominated microbiota was associated specifically with atopy- associated phenotypes. Analysis of paired house dust and nasal samples indicated that 12 month olds with low wheeze and atopy incidence exhibited the largest number of shared bacterial taxa with their environment. Conclusion: Nasal microbiota development over the course of early childhood and composition at age 3 years are associated with longitudinal respiratory phenotypes. These data provide evidence supporting an early -life window of airway microbiota development that is influenced by environmental microbial exposures in infancy and associates with wheeze- and atopy-associated respiratory phenotypes through age 7 years. (J Allergy Clin Immunol 2024;153:1563-73.)