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Species turnover within cystic fibrosis lung microbiota is indicative of acute pulmonary exacerbation onset

Leah Cuthbertson, Lauren Hatfield, Helen Gavillet, Michelle Hardman, Ryan Marsh, Damian W. Rivett, Christopher van der Gast

Microbiome, Volume: 13, Start page: 140

Swansea University Author: Michelle Hardman

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Abstract

Background: Acute pulmonary exacerbations (PEx) are associated with increased morbidity and earlier mortality for people living with cystic fibrosis (pwCF). The most common causes of PEx in CF are by bacterial infection and concomitant inflammation leading to progressive airway damage. To draw atten...

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Published in: Microbiome
ISSN: 2049-2618
Published: Springer Nature 2025
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa69653
Abstract: Background: Acute pulmonary exacerbations (PEx) are associated with increased morbidity and earlier mortality for people living with cystic fibrosis (pwCF). The most common causes of PEx in CF are by bacterial infection and concomitant inflammation leading to progressive airway damage. To draw attention to the seriousness of PEx they have been labelled as ‘lung attacks’, much like a ‘heart attack’ for acute myocardial infarction. Treatment typically starts when a pwCF presents with worsening respiratory symptoms. Hence, there is a pressing need to identify indicative biomarkers of PEx onset to allow more timely intervention. Set within an ecological framework, we investigated temporal microbiota dynamics to connect changes in the lung microbiota of pwCF to changes in disease states across a PEx event. Results: Species-time relationships (STR) describe how the richness of a community changes with time, here STRs were used to assess temporal turnover (w) within the lung microbiota of each pwCF (n = 12, mean sample duration 315.9 ± 42.7 days). STRs were characterised by high interpatient variability, indicating that turnover and hence temporal organization are a personalized feature of the CF lung microbiota. Greater turnover was found to be significantly associated with greater change in lung function with time. When microbiota turnover was examined at a finer scale across each pwCF time series, w-values could clearly be observed to increase in the exacerbation period, then peaking within the treatment period, demonstrating that increases in turnover were not solely a result of perturbations caused by PEx antibiotic interventions. STR w-values have been found to have a remarkable degree of similarity for different organisms, in a variety of habitats and ecosystems, and time lengths (typically not exceeding w = 0.5). Here, we found w-values soon increased beyond that. It was therefore possible to use the departure from that expected norm up to start of treatment to approximate onset of PEx in days (21.2 ± 8.9 days across the study participants). Conclusions: Here, we illustrate that changes in turnover of the lung microbiota of pwCF can be indicative of PEx onset in considerable advance of when treatment would normally be initiated. This offers translational potential to enable early detection of PEx and consequent timely intervention.
Keywords: Cystic fibrosis; Lung microbiome; Temporal dynamics; Island biogeography; Species-time relationships; Microbiome ecology; Species turnover; Lung function; Pulmonary exacerbation
College: Faculty of Medicine, Health and Life Sciences
Funders: This work was supported by the Cystic Fibrosis Trust (VIA 045) awarded to CvdG and DWR, and by the UK Natural Environment Research Council (NE/H019456/1) awarded to CvdG.
Start Page: 140