Cuthbertson, Leah, Rogers, Geraint B., Walker, Alan W., Oliver, Anna, Green, Laura E., Daniels, Thomas W. V., Carroll, Mary P., Parkhill, Julian, Bruce, Kenneth D. and van der Gast, Christopher J. (2016) Respiratory microbiota resistance and resilience to pulmonary exacerbation and subsequent antimicrobial intervention. The ISME Journal, 10 (5). pp. 1081-1091. doi:10.1038/ismej.2015.198 ISSN 1751-7362.

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Abstract

Pulmonary symptoms in cystic fibrosis (CF) begin in early life with chronic lung infections and concomitant airway inflammation leading to progressive loss of lung function. Gradual pulmonary function decline is interspersed with periods of acute worsening of respiratory symptoms known as CF pulmonary exacerbations (CFPEs). Cumulatively, CFPEs are associated with more rapid disease progression. In this study multiple sputum samples were collected from adult CF patients over the course of CFPEs to better understand how changes in microbiota are associated with CFPE onset and management. Data were divided into five clinical periods: pre-CFPE baseline, CFPE, antibiotic treatment, recovery, and post-CFPE baseline. Samples were treated with propidium monoazide prior to DNA extraction, to remove the impact of bacterial cell death artefacts following antibiotic treatment, and then characterised by 16S rRNA gene-targeted high-throughput sequencing. Partitioning CF microbiota into core and rare groups revealed compositional resistance to CFPE and resilience to antibiotics interventions. Mixed effects modelling of core microbiota members revealed no significant negative impact on the relative abundance of Pseudomonas aeruginosa across the exacerbation cycle. Our findings have implications for current CFPE management strategies, supporting reassessment of existing antimicrobial treatment regimens, as antimicrobial resistance by pathogens and other members of the microbiota may be significant contributing factors.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine
Divisions:	Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH):	Cystic fibrosis -- Treatment
Journal or Publication Title:	The ISME Journal
Publisher:	Nature Publishing Group
ISSN:	1751-7362
Official Date:	May 2016
Dates:	Date Event May 2016 Published 10 November 2015 Available 22 September 2015 Accepted 27 July 2015 Submitted
Volume:	10
Number:	5
Page Range:	pp. 1081-1091
DOI:	10.1038/ismej.2015.198
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Date of first compliant deposit:	14 July 2016
Date of first compliant Open Access:	14 July 2016
Funder:	Natural Environment Research Council (Great Britain) (NERC), Wellcome Trust (London, England), Anna Trust, Scotland. Rural and Environment Science and Analytical Services (RESAS)
Grant number:	NE/H019456/1 (NERC), 098051 (WT), KB2008 (AT)

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