Respiratory microbiota resistance and resilience to pulmonary exacerbation and subsequent antimicrobial intervention

Leah Cuthbertson, Geraint B. Rogers, Alan W. Walker, Anna Oliver, Laura E. Green, Thomas W. V. Daniels, Mary P. Carroll, Julian Parkhill, Kenneth D. Bruce, Christopher J. van der Gast

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1081-1091
Number of pages11
JournalThe ISME Journal
Volume10
Issue number5
Early online date10 Nov 2015
DOIs
Publication statusPublished - May 2016

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Microbiota
antibiotics
anti-infective agents
lungs
Lung
cystic fibrosis
Cystic Fibrosis
artifact
relative abundance
partitioning
pathogen
DNA
lung function
gene
Anti-Bacterial Agents
signs and symptoms (animals and humans)
modeling
microbiome
Pseudomonas aeruginosa
disease course

Cite this

Cuthbertson, L., Rogers, G. B., Walker, A. W., Oliver, A., Green, L. E., Daniels, T. W. V., ... van der Gast, C. J. (2016). Respiratory microbiota resistance and resilience to pulmonary exacerbation and subsequent antimicrobial intervention. The ISME Journal, 10(5), 1081-1091. https://doi.org/10.1038/ismej.2015.198

Respiratory microbiota resistance and resilience to pulmonary exacerbation and subsequent antimicrobial intervention. / 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.; van der Gast, Christopher J.

In: The ISME Journal, Vol. 10, No. 5, 05.2016, p. 1081-1091.

Research output: Contribution to journalArticle

Cuthbertson, L, Rogers, GB, Walker, AW, Oliver, A, Green, LE, Daniels, TWV, Carroll, MP, Parkhill, J, Bruce, KD & van der Gast, CJ 2016, 'Respiratory microbiota resistance and resilience to pulmonary exacerbation and subsequent antimicrobial intervention', The ISME Journal, vol. 10, no. 5, pp. 1081-1091. https://doi.org/10.1038/ismej.2015.198
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. ; van der Gast, Christopher J. / Respiratory microbiota resistance and resilience to pulmonary exacerbation and subsequent antimicrobial intervention. In: The ISME Journal. 2016 ; Vol. 10, No. 5. pp. 1081-1091.
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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.",
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