lunes, 8 de julio de 2013

Changes in Cystic Fibrosis Airway Microbiota at Pulmonary Exacerbation (thoracic)

Lisa A. Carmody, Jiangchao Zhao, Patrick D. Schloss, Joseph F. Petrosino, Susan Murray, Vincent B. Young, Jun Z. Li, and John J. LiPuma "Changes in Cystic Fibrosis Airway Microbiota at Pulmonary Exacerbation", Annals of the American Thoracic Society, Vol. 10, No. 3 (2013), pp. 179-187.

Changes in Cystic Fibrosis Airway Microbiota at Pulmonary Exacerbation

Lisa A. Carmody¹ *, Jiangchao Zhao¹ *, Patrick D. Schloss², Joseph F. Petrosino³, Susan Murray⁴, Vincent B. Young²^,⁵, Jun Z. Li⁶, and John J. LiPuma¹

+ Author Affiliations

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.

KEYWORDS: lung microbiome, cystic fibrosis exacerbation, Pseudomonas, Gemella

*These authors contributed equally to this work.

Correspondence and requests for reprints should be addressed to John J. LiPuma, M.D., Division of Pediatrics, University of Michigan Medical School, 1150 W. Medical Center Drive, SPC 5646, Ann Arbor, MI 48109. E-mail: jlipuma@med.umich.edu

Accepted February 16, 2013
Received November 21, 2012

This work was supported by National Institutes of Health, National Heart, Lung and Blood Institute grants 1RC1HL100809–01 (J.J.L., V.B.Y., and J.Z.L.) and U01HL098961, R01HG004906, and P30DK034933 (V.B.Y.); by CTSA grant UL1RR024986; by the Cystic Fibrosis Foundation (J.J.L.); and by the Charles Woodson Pediatric Research Fund.

Author Contributions: L.A.C., J.Z., and J.J.L. conceived and designed the study; L.A.C., J.Z., and J.F.P. performed experiments; L.A.C., J.Z., P.D.S., S.M., J.Z.L., and J.J.L. interpreted results; L.A.C., J.Z., P.D.S., S.M., V.B.Y., J.Z.L., and J.J.L. analyzed data and wrote the manuscript.

This article has an online supplement, which is accessible from this issue’s table of contents at www.atsjournals.org

Author disclosures are available with the text of this article at www.atsjournals.org.