• Bosch Astrid A T M AATM 1 Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, the Nethe, de Steenhuijsen Piters Wouter A A WAA 1 Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utre, Marlies A van Houten, Mei Ling J N Chu, Giske Biesbroek, Jolanda Kool, Paula Pernet, Pieter-Kees C M de Groot, Eijkemans Marinus J C MJC 7 Biostatistics and Research Support, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Nether, Keijser Bart J F BJF 5 Microbiology and Systems Biology Group, Netherlands Organisation for Applied Scientific Research, Zeist, the Netherlands. , Sanders Elisabeth A M EAM 1 Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, the Net, and Debby Bogaert.
• 1 Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, the Netherlands.
• Am. J. Respir. Crit. Care Med. 2017 Dec 15; 196 (12): 1582-1590.

RationalePerinatal 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.ObjectivesTo 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.MethodsIn 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 ResultsUsing 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.ConclusionsOur 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.

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