Abstract
The structure and dynamics of bacterial communities in the airways of persons with cystic fibrosis (CF) remain largely unknown. We characterized the bacterial communities in 126 sputum samples representing serial collections spanning 8-9 y from six age-matched male CF patients. Sputum DNA was analyzed by bar-coded pyrosequencing of the V3-V5 hypervariable region of the 16S rRNA gene, defining 662 operational taxonomic units (OTUs) from >633,000 sequences. Bacterial community diversity decreased significantly over time in patients with typically progressive lung disease but remained relatively stable in patients with a mild lung disease phenotype. Antibiotic use, rather than patient age or lung function, was the primary driver of decreasing diversity. Interpatient variability in community structure exceeded intrapatient variability in serial samples. Antibiotic treatment was associated with pronounced shifts in community structure, but communities showed both short- and long-term resilience after antibiotic perturbation. There was a positive correlation between OTU occurrence and relative abundance, with a small number of persistent OTUs accounting for the greatest abundance. Significant changes in community structure, diversity, or total bacterial density at the time of pulmonary exacerbation were not observed. Despite decreasing community diversity in patients with progressive disease, total bacterial density remained relatively stable over time. These findings show the critical relationship between airway bacterial community structure, disease stage, and clinical state at the time of sample collection. These features are the key parameters with which to assess the complex ecology of the CF airway.
MeSH Terms
Adolescent
Adult
Aging/drug effects
Anti-Bacterial Agents/pharmacology,therapeutic use
Bacteria/classification,drug effects,growth & development
Bacterial Load/drug effects
Biodiversity
Cystic Fibrosis/drug therapy,microbiology,physiopathology
Disease Progression
Humans
Lung/drug effects,microbiology,pathology,physiopathology
Male
Metagenome/drug effects
Principal Component Analysis
Respiratory Function Tests
Sputum/drug effects,microbiology
Young Adult
Chemicals
Anti-Bacterial Agents
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Zhao Jiangchao
Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Schloss Patrick D
Kalikin Linda M
Carmody Lisa A
Foster Bridget K
Petrosino Joseph F
Cavalcoli James D
VanDevanter Donald R
Murray Susan
Li Jun Z
Young Vincent B
LiPuma John J
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