Development of the Nasopharyngeal Microbiota in Infants with Cystic Fibrosis.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
1 Department of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.
Sabine M P J
SM
Prevaes
1 Department of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.
Karin M
KM
de Winter-de Groot
2 Department of Pediatric Pulmonology and Allergology, Sophia Children's Hospital, Erasmus University Medical Center, Rotterdam, the Netherlands; and.
Hettie M
HM
Janssens
1 Department of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.
Wouter A A
WA
de Steenhuijsen Piters
1 Department of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.
Gerdien A
GA
Tramper-Stranders
1 Department of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.
Anne L
AL
Wyllie
1 Department of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.
Raiza
R
Hasrat
2 Department of Pediatric Pulmonology and Allergology, Sophia Children's Hospital, Erasmus University Medical Center, Rotterdam, the Netherlands; and.
Harm A
HA
Tiddens
3 Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Rotterdam, the Netherlands.
Mireille
M
van Westreenen
1 Department of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.
Cornelis K
CK
van der Ent
1 Department of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.
Elisabeth A M
EA
Sanders
1 Department of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.
Debby
D
Bogaert
D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D019117:Burkholderia / Q000235:genetics; D019121:Burkholderia Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D002353:Carrier State / Q000453:epidemiology / Q000382:microbiology*; D016022:Case-Control Studies; D015331:Cohort Studies; D003352:Corynebacterium / Q000235:genetics; D003354:Corynebacterium Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D003550:Cystic Fibrosis / Q000453:epidemiology / Q000382:microbiology*; D004269:DNA, Bacterial / Q000235:genetics*; D004755:Enterobacteriaceae / Q000235:genetics; D004756:Enterobacteriaceae Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D005260:Female; D006192:Haemophilus Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D006193:Haemophilus influenzae / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D064307:Microbiota / Q000235:genetics*; D009016:Moraxella / Q000235:genetics; D045828:Moraxellaceae Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D009305:Nasopharynx / Q000382:microbiology*; D011446:Prospective Studies; D012336:RNA, Ribosomal, 16S / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics; D013290:Streptococcal Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D034361:Streptococcus mitis / Q000235:genetics
D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D012336:RNA, Ribosomal, 16S
cystic fibrosis; healthy controls; longitudinal; microbiota; nasopharynx