Longitudinal assessment of sputum microbiome by sequencing of the 16S rRNA gene in non-cystic fibrosis bronchiectasis patients.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Michael J
http://orcid.org/0000-0002-4002-1506
MJ
Cox
National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Elena M
EM
Turek
Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom.
Catherine
C
Hennessy
National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Ghazala K
GK
Mirza
National Heart and Lung Institute, Imperial College London, London, United Kingdom.|Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom.
Phillip L
PL
James
Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom.
Meg
M
Coleman
Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom.
Andrew
A
Jones
Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom.
Robert
R
Wilson
National Heart and Lung Institute, Imperial College London, London, United Kingdom.|Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom.
Diana
D
Bilton
National Heart and Lung Institute, Imperial College London, London, United Kingdom.|Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom.
William O C
WO
Cookson
National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Miriam F
MF
Moffatt
National Heart and Lung Institute, Imperial College London, London, United Kingdom.|Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom.
Michael R
MR
Loebinger
D000368:Aged; D001987:Bronchiectasis / Q000150:complications* / Q000175:diagnosis / Q000209:etiology; D001991:Bronchitis / Q000175:diagnosis* / Q000209:etiology* / Q000503:physiopathology; D003430:Cross-Sectional Studies; D006801:Humans; D056186:Metagenomics / Q000379:methods; D064307:Microbiota; D008875:Middle Aged; D012336:RNA, Ribosomal, 16S; D012129:Respiratory Function Tests; D012307:Risk Factors; D013183:Sputum / Q000382:microbiology*; D014057:Tomography, X-Ray Computed
D012336:RNA, Ribosomal, 16S