Changes in Cystic Fibrosis Airway Microbiota at Pulmonary Exacerbation

Abstract Rationale In persons with cystic fibrosis (CF), repeated exacerbations of pulmonary symptoms are associated with a progressive decline in lung function. Changes in the airway microbiota around the time of exacerbations are not well understood. Objectives To characterize changes in airway bacterial communities around the time of exacerbations and to identify predictors for these changes. Methods DNA prepared from 68 paired baseline and exacerbation sputum samples collected from 28 patients with CF were subjected to barcoded 16S rRNA gene pyrosequencing. Bacterial density was calculated by quantitative PCR. Measurements and Main Results Overall, significant differences in bacterial community diversity and bacterial density between baseline and exacerbation samples were not observed. However, considerable changes in community structures were observed in a subset of patients. In these patients, the dominant taxa and initial level of community diversity were significant predictors of the magnitude of community structure changes at exacerbation. Pseudomonas-dominant communities became more diverse at exacerbation compared with communities with other or no dominant species. The relative abundance of Gemella increased in 24 (83%) of 29 samples at exacerbation and was found to be the most discriminative genus between baseline and exacerbation samples. Conclusions The magnitude of changes in the CF lung microbiota around the time of exacerbation was found to be largely dependent on community diversity and composition at baseline. Certain genera appear to play important roles in driving change in airway bacterial community composition at exacerbation. Gemella might play a direct role in and/or be a biomarker for pulmonary exacerbation.