Maturation of the Infant Respiratory Microbiota, Environmental Drivers, and Health Consequences. A Prospective Cohort Study.

RATIONALE: Perinatal and postnatal influences are presumed important drivers of the early-life respiratory microbiota composition. We hypothesized that the respiratory microbiota composition and development in infancy is affecting microbiota stability and thereby resistance against respiratory tract infections (RTIs) over time. OBJECTIVES: To investigate common environmental drivers, including birth mode, feeding type, antibiotic exposure, and crowding conditions, in relation to respiratory tract microbiota maturation and stability, and consecutive risk of RTIs over the first year of life. METHODS: In a prospectively followed cohort of 112 infants, we characterized the nasopharyngeal microbiota longitudinally from birth on (11 consecutive sample moments and the maximum three RTI samples per subject; in total, n = 1,121 samples) by 16S-rRNA gene amplicon sequencing. MEASUREMENTS AND MAIN RESULTS: Using a microbiota-based machine-learning algorithm, we found that children experiencing a higher number of RTIs in the first year of life already demonstrate an aberrant microbial developmental trajectory from the first month of life on as compared with the reference group (0-2 RTIs/yr). The altered microbiota maturation process coincided with decreased microbial community stability, prolonged reduction of Corynebacterium and Dolosigranulum, enrichment of Moraxella very early in life, followed by later enrichment of Neisseria and Prevotella spp. Independent drivers of these aberrant developmental trajectories of respiratory microbiota members were mode of delivery, infant feeding, crowding, and recent antibiotic use. CONCLUSIONS: Our results suggest that environmental drivers impact microbiota development and, consequently, resistance against development of RTIs. This supports the idea that microbiota form the mediator between early-life environmental risk factors for and susceptibility to RTIs over the first year of life.

Development of Upper Respiratory Tract Microbiota in Infancy is Affected by Mode of Delivery.

Birth by Caesarian section is associated with short- and long-term respiratory morbidity. We hypothesized that mode of delivery affects the development of the respiratory microbiota, thereby altering its capacity to provide colonization resistance and consecutive pathobiont overgrowth and infections. Therefore, we longitudinally studied the impact of mode of delivery on the nasopharyngeal microbiota development from birth until six months of age in a healthy, unselected birth cohort of 102 children (n=761 samples). Here, we show that the respiratory microbiota develops within one day from a variable mixed bacterial community towards a Streptococcus viridans-predominated profile, regardless of mode of delivery. Within the first week, rapid niche differentiation had occurred; initially with in most infants Staphylococcus aureus predominance, followed by differentiation towards Corynebacterium pseudodiphteriticum/propinquum, Dolosigranulum pigrum, Moraxella catarrhalis/nonliquefaciens, Streptococcus pneumoniae, and/or Haemophilus influenzae dominated communities. Infants born by Caesarian section showed a delay in overall development of respiratory microbiota profiles with specifically reduced colonization with health-associated commensals like Corynebacterium and Dolosigranulum, thereby possibly influencing respiratory health later in life.