title: Associations between Gut Microbial Colonization in Early Life and Respiratory Outcomes in Cystic Fibrosis.
abstract: OBJECTIVE
  To examine patterns of microbial colonization of the respiratory and intestinal tracts in early life in infants with cystic fibrosis (CF) and their associations with breastfeeding and clinical outcomes.
  
  
  METHODS
  A comprehensive, prospective longitudinal analysis of the upper respiratory and intestinal microbiota in a cohort of infants and young children with CF followed from birth was performed. Genus-level microbial community composition was characterized using 16S-targeted pyrosequencing, and relationships with exposures and outcomes were assessed using linear mixed-effects models, time-to-event analysis, and principal components analysis.
  
  
  RESULTS
  Sequencing of 120 samples from 13 subjects collected from birth to 34 months revealed relationships between breastfeeding, microbial diversity in the respiratory and intestinal tracts, and the timing of onset of respiratory complications, including exacerbations and colonization with Pseudomonas aeruginosa. Fluctuations in the abundance of specific bacterial taxa preceded clinical outcomes, including a significant decrease in bacteria of the genus Parabacteroides within the intestinal tract prior to the onset of chronic P aeruginosa colonization. Specific assemblages of bacteria in intestinal samples, but not respiratory samples, were associated with CF exacerbation in early life, indicating that the intestinal microbiome may play a role in lung health.
  
  
  CONCLUSIONS
  Our findings relating breastfeeding to respiratory outcomes, gut diversity to prolonged periods of health, and specific bacterial communities in the gut prior to respiratory complications in CF highlight a connection between the intestinal microbiome and health and point to potential opportunities for antibiotic or probiotic interventions. Further studies in larger cohorts validating these findings are needed.
authors.affiliation: Computational Genetics Laboratory, Institute for Quantitative Biomedical Sciences, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH; Department of Epidemiology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH.
authors.forename: Anne G
authors.initials: AG
authors.lastname: Hoen
authors.affiliation: Computational Genetics Laboratory, Institute for Quantitative Biomedical Sciences, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Division of Allergy and Pediatric Pulmonology, Department of Pediatrics, Dartmouth-Hitchcock Medical Center, Lebanon, NH.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Moulton
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH.
authors.forename: George A
authors.initials: GA
authors.lastname: O'Toole
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH.
authors.forename: Molly L
authors.initials: ML
authors.lastname: Housman
authors.affiliation: Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS.
authors.forename: Devin C
authors.initials: DC
authors.lastname: Koestler
authors.affiliation: Division of Allergy and Pediatric Pulmonology, Department of Pediatrics, Dartmouth-Hitchcock Medical Center, Lebanon, NH.
authors.forename: Margaret F
authors.initials: MF
authors.lastname: Guill
authors.affiliation: Computational Genetics Laboratory, Institute for Quantitative Biomedical Sciences, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH.
authors.forename: Jason H
authors.initials: JH
authors.lastname: Moore
authors.affiliation: Division of Global Health, Department of Pediatrics, Massachusetts General Hospital, Boston, MA.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Hibberd
authors.affiliation: Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, Marine Biological Laboratory, Woods Hole, MA.
authors.forename: Hilary G
authors.initials: HG
authors.lastname: Morrison
authors.affiliation: Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, Marine Biological Laboratory, Woods Hole, MA.
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Sogin
authors.affiliation: Department of Epidemiology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Karagas
authors.affiliation: Division of Neonatology, Department of Pediatrics, Dartmouth-Hitchcock Medical Center, Lebanon, NH. Electronic address: Juliette.C.Madan@Dartmouth.Edu.
authors.forename: Juliette C
authors.initials: JC
authors.lastname: Madan
mesh_terms: D001942:Breast Feeding; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000382:microbiology*; D018450:Disease Progression; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007422:Intestines / Q000382:microbiology*; D008137:Longitudinal Studies; D064307:Microbiota; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000150:complications; D011550:Pseudomonas aeruginosa; D012137:Respiratory System / Q000382:microbiology*
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