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

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

doi:10.1038/ismej.2015.198

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.

Highlights

Cystic fibrosis (CF) is a common recessive genetic disorder, primarily of Caucasians, affecting more than 8000 children and adults in the UK and an estimated 100 000 globally (Davies et al, 2014)
This gradual decline in pulmonary function is interspersed with periods of acute worsening of respiratory symptoms known as CF pulmonary exacerbations (CFPEs) (Sibley et al, 2008)
Treatment, and (R) recovery (Zhao et al, 2012; Price et al, 2013). Set within this BETR classification, Materials and methods studies have provided useful insights including a clear demonstration that CFPE do not result from Patients and clinical samples increased total bacterial density or density of This study was undertaken with the local ethical a specific recognised CF pathogen, such as approval from Southampton and South West

Summary

Introduction

Cystic fibrosis (CF) is a common recessive genetic disorder, primarily of Caucasians, affecting more than 8000 children and adults in the UK and an estimated 100 000 globally (Davies et al, 2014). Studies have an indicator of worsening symptoms, it has been been based in the main on point samples from revealed that short-term changes in lung function subsets and different combinations of the clinical show little effect on the sensitivity or specificity of periods defined above Treatment, and (R) recovery (Zhao et al, 2012; Price et al, 2013) Set within this BETR classification, Materials and methods studies have provided useful insights including a clear demonstration that CFPE do not result from Patients and clinical samples increased total bacterial density or density of This study was undertaken with the local ethical a specific recognised CF pathogen, such as approval from Southampton and South West. The start and end of CFPE were identified by treating clinicians, and were defined for the purpose of this study as the period of time where patients received clinical intervention in the form of antibiotic treatment. The relevant barcode information for each sample is shown in An expectation for patterns of lung function (FEV1)

Pa Vp Sp

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Findings

Discussion