Research Article: Longitudinal assessment of sputum microbiome by sequencing of the 16S rRNA gene in non-cystic fibrosis bronchiectasis patients

Date Published: February 7, 2017

Publisher: Public Library of Science

Author(s): Michael J. Cox, Elena M. Turek, Catherine Hennessy, Ghazala K. Mirza, Phillip L. James, Meg Coleman, Andrew Jones, Robert Wilson, Diana Bilton, William O. C. Cookson, Miriam F. Moffatt, Michael R. Loebinger, Marie-Joelle Virolle.


Bronchiectasis is accompanied by chronic bronchial infection that may drive disease progression. However, the evidence base for antibiotic therapy is limited. DNA based methods offer better identification and quantification of microbial constituents of sputum than standard clinical culture and may help inform patient management strategies. Our study objective was to determine the longitudinal variability of the non-cystic fibrosis (CF) bronchiectasis microbiome in sputum with respect to clinical variables. Eighty-five patients with non-CF bronchiectasis and daily sputum production were recruited from outpatient clinics and followed for six months. Monthly sputum samples and clinical measurements were taken, together with additional samples during exacerbations. 16S rRNA gene sequencing of the sputum microbiota was successful for 381 samples from 76 patients and analysed in conjunction with clinical data.

Microbial communities were highly individual in composition and stability, usually with limited diversity and often containing multiple pathogens. When compared to DNA sequencing, microbial culture had restricted sensitivity in identifying common pathogens such as Pseudomonas aeruginosa, Haemophilus influenzae, Moraxella catarrhalis. With some exceptions, community characteristics showed poor correlations with clinical features including underlying disease, antibiotic use and exacerbations, with the subject showing the strongest association with community structure. When present, the pathogens mucoid Pseudomonas aeruginosa and Haemophilus influenzae may also shape the structure of the rest of the microbial community.

The use of microbial community analysis of sputum added to information from microbial culture. A simple model of exacerbations driven by bacterial overgrowth was not supported, suggesting a need for revision of principles for antibiotic therapy. In individual patients, the management of chronic bronchial infection may be improved by therapy specific to their microbiome, taking into account pathogen load, community stability, and acute and chronic community responses to antibiotics.

Partial Text

Bronchiectasis is characterised by abnormal dilated thick-walled bronchi and is often accompanied by chronic bronchial infection. Patients with advanced disease may produce copious volumes of purulent sputum and lung function may be severely and progressively impaired. The prevalence of non-CF bronchiectasis in the US has been estimated at 272 per 100 000 persons over 75 years of age and hospitalisation rates are increasing [1].

The study shows substantial complexity in the airway microbiome in patients with chronic bronchial infection, with frequent mixed infections and potentially important discrepancies between DNA sequencing results and classical clinical culture. The structure of microbial communities within patients was highly individual, relating only weakly to underlying disease, and often stable over the six months of the study despite the use of antibiotics and changes in clinical state.




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