Airway microbial diversity is decreased in young children with cystic fibrosis compared to healthy controls but improved with CFTR modulation
Andrea Hahn,
Aszia Burrell,
Emily Ansusinha,
Diane Peng,
Hollis Chaney,
Iman Sami,
Geovanny F. Perez,
Anastassios C. Koumbourlis,
Robert McCarter,
Robert J. Freishtat,
Keith A. Crandall,
Edith T. Zemanick
Affiliations
Andrea Hahn
Division of Infectious Diseases, Children's National Hospital, Washington, DC, USA; Center for Genetic Medicine Research, Children's National Research Institute, Washington, DC, USA; Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, USA; Corresponding author.
Aszia Burrell
Center for Genetic Medicine Research, Children's National Research Institute, Washington, DC, USA
Emily Ansusinha
Division of Infectious Diseases, Children's National Hospital, Washington, DC, USA
Diane Peng
George Washington University School of Medicine and Health Sciences, Washington, DC, USA
Hollis Chaney
Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, USA; Division of Pulmonary and Sleep Medicine, Children's National Hospital, Washington, DC, USA
Iman Sami
Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, USA; Division of Pulmonary and Sleep Medicine, Children's National Hospital, Washington, DC, USA
Geovanny F. Perez
Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, USA; Division of Pulmonary and Sleep Medicine, Children's National Hospital, Washington, DC, USA
Anastassios C. Koumbourlis
Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, USA; Division of Pulmonary and Sleep Medicine, Children's National Hospital, Washington, DC, USA
Robert McCarter
Center for Translational Research, Children's National Research Institute, Washington, DC, USA
Robert J. Freishtat
Center for Genetic Medicine Research, Children's National Research Institute, Washington, DC, USA; Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, USA; Division of Emergency Medicine, Children's National Hospital, Washington, DC, USA
Keith A. Crandall
Computational Biology Institute, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, George Washington University, Washington, DC, USA
Edith T. Zemanick
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Background: Culture-independent next generation sequencing has identified diverse microbial communities within the cystic fibrosis (CF) airway. The study objective was to test for differences in the upper airway microbiome of children with CF and healthy controls and age-related differences in children with CF. Methods: Oropharyngeal swabs and clinical data were obtained from 25 children with CF and 50 healthy controls aged ≤6 years. Bacterial DNA was amplified and sequenced for the V4 region of 16S rRNA marker-gene. Alpha diversity was measured using operational taxonomic units (OTUs), Shannon diversity, and the inverse Simpson's index. Beta diversity was measured using Morisita-Horn and Bray-Curtis and Jaccard distances. General linear models were used for comparison of alpha diversity measures between groups to account for differences in demographics and exposures. Mixed effects general linear models were used for longitudinal comparisons 1) between children with CF of different ages and 2) between children with CF receiving CF transmembrane conductance regulator (CFTR) modulators, children with CF not receiving CFTR modulators, and healthy controls to adjust for repeated measures per subject. Results: Children with CF were more likely to have received antibiotics in the prior year than healthy controls (92% vs 24%, p 2 years of age, there was a significant trend in increasing alpha diversity measures between children with CF not receiving CFTR modulators, children with CF receiving CFTR modulators, and healthy controls: OTUs 63.7 vs 74.7 vs 97.6, p < 0.001; Shannon 2.11 vs 2.34 vs 2.56, p < 0.001; inverse Simpson 5.78 vs 7.23 vs 7.96, p < 0.001. Conclusions: Children with CF have lower bacterial diversity and different composition of organisms compared with healthy controls. This appears to start in early childhood, is possibly related to the use of antibiotics, and may be partially corrected with the use of CFTR modulators.
