Development of the Nasopharyngeal Microbiota in Infants with Cystic Fibrosis

• Published in: American journal of respiratory and critical care medicine Vol. 193; no. 5; pp. 504 - 515
• Main Authors: Prevaes, Sabine M. P. J., de Winter-de Groot, Karin M., Janssens, Hettie M., de Steenhuijsen Piters, Wouter A. A., Tramper-Stranders, Gerdien A., Wyllie, Anne L., Hasrat, Raiza, Tiddens, Harm A., van Westreenen, Mireille, van der Ent, Cornelis K., Sanders, Elisabeth A. M., Bogaert, Debby
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01.03.2016
• Subjects: Anti-Bacterial Agents - therapeutic use; Burkholderia - genetics; Burkholderia Infections - drug therapy; Burkholderia Infections - epidemiology; Burkholderia Infections - microbiology; Carrier State - epidemiology; Carrier State - microbiology; Case-Control Studies; Cohort Studies; Corynebacterium - genetics; Corynebacterium Infections - drug therapy; Corynebacterium Infections - epidemiology; Corynebacterium Infections - microbiology; Cystic Fibrosis - epidemiology; Cystic Fibrosis - microbiology; DNA, Bacterial - genetics; Enterobacteriaceae - genetics; Enterobacteriaceae Infections - drug therapy; Enterobacteriaceae Infections - epidemiology; Enterobacteriaceae Infections - microbiology; Female; Haemophilus Infections - drug therapy; Haemophilus Infections - epidemiology; Haemophilus Infections - microbiology; Haemophilus influenzae - genetics; Humans; Infant; Infant, Newborn; Male; Microbiota - genetics; Moraxella - genetics; Moraxellaceae Infections - drug therapy; Moraxellaceae Infections - epidemiology; Moraxellaceae Infections - microbiology; Nasopharynx - microbiology; Prospective Studies; Real-Time Polymerase Chain Reaction; RNA, Ribosomal, 16S - genetics; Staphylococcal Infections - drug therapy; Staphylococcal Infections - epidemiology; Staphylococcal Infections - microbiology; Staphylococcus aureus - genetics; Streptococcal Infections - drug therapy; Streptococcal Infections - epidemiology; Streptococcal Infections - microbiology; Streptococcus mitis - genetics; microbiota; longitudinal; nasopharynx; healthy controls; cystic fibrosis
• DOI: 10.1164/rccm.201509-1759OC
• ISSN: 1073-449X

Cystic fibrosis (CF) is characterized by early structural lung disease caused by pulmonary infections. The nasopharynx of infants is a major ecological reservoir of potential respiratory pathogens. To investigate the development of nasopharyngeal microbiota profiles in infants with CF compared with those of healthy control subjects during the first 6 months of life. We conducted a prospective cohort study, from the time of diagnosis onward, in which we collected questionnaires and 324 nasopharynx samples from 20 infants with CF and 45 age-matched healthy control subjects. Microbiota profiles were characterized by 16S ribosomal RNA-based sequencing. We observed significant differences in microbial community composition (P < 0.0002 by permutational multivariate analysis of variance) and development between groups. In infants with CF, early Staphylococcus aureus and, to a lesser extent, Corynebacterium spp. and Moraxella spp. dominance were followed by a switch to Streptococcus mitis predominance after 3 months of age. In control subjects, Moraxella spp. enrichment occurred throughout the first 6 months of life. In a multivariate analysis, S. aureus, S. mitis, Corynebacterium accolens, and bacilli were significantly more abundant in infants with CF, whereas Moraxella spp., Corynebacterium pseudodiphtericum and Corynebacterium propinquum and Haemophilus influenzae were significantly more abundant in control subjects, after correction for age, antibiotic use, and respiratory symptoms. Antibiotic use was independently associated with increased colonization of gram-negative bacteria such as Burkholderia spp. and members of the Enterobacteriaceae bacteria family and reduced colonization of potential beneficial commensals. From diagnosis onward, we observed distinct patterns of nasopharyngeal microbiota development in infants with CF under 6 months of age compared with control subjects and a marked effect of antibiotic therapy leading toward a gram-negative microbial composition.