4.7 Article

Microbial Community Composition in Explanted Cystic Fibrosis and Control Donor Lungs

Journal

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fcimb.2021.764585

Keywords

microbiota (16S rRNA); cystic fibrosis; lung explant; disease; health

Funding

  1. European Union Innovative Medicines Initiative [115721]
  2. Health and Social Care Northern Ireland Research and Development office [COM4978/14]
  3. FWO [12G8718N, G083818N]
  4. KU Leuven [C24/18/073, C24/050]
  5. Broere foundation
  6. Forton grant of the Koning Boudewijn Stiching
  7. EFPIA (Novartis )
  8. EFPIA (Polyphor)

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This study analyzed the microbiota in the lung tissue and airway luminal mucus of PWCF patients and compared them to disease characteristics and lung damage. The results showed significant differences in microbial communities between different groups, but also overlap. The luminal mucus of PWCF had lower microbial diversity and higher dominance. Variability in ecological parameters was observed both between and within patients, but no clear relationship was found between ecological parameters and disease characteristics.
To date, investigations of the microbiota in the lungs of people with Cystic Fibrosis (PWCF) have primarily focused on microbial community composition in luminal mucus, with fewer studies observing the microbiota in tissue samples from explanted lung tissue. Here, we analysed both tissue and airway luminal mucus samples extracted from whole explanted lungs of PWCF and unused donor lungs. We determined if the lung microbiota in end-stage CF varied within and between patients, was spatially heterogeneous and related to localized structural damage. Microbial community composition was determined by Illumina MiSeq sequencing and related to the CF-Computed Tomography (CT) score and features of end-stage lung disease on micro-CT. Ninety-eight CF tissue (n=11 patients), 20 CF luminal mucus (n=8 patients) and 33 donor tissue (n=4 patients) samples were analysed. Additionally, we compared 20 paired CF tissue and luminal mucus samples that enabled a direct geographical comparison of the microbiota in these two niches. Significant differences in microbial communities were apparent between the 3 groups. However, overlap between the three groups, particularly between CF and donor tissue and CF tissue and CF luminal mucus was also observed. Microbial diversity was lower in CF luminal mucus compared to CF tissue, with dominance higher in luminal mucus. For both CF and donor tissue, intra- and inter-patient variability in ecological parameters was observed. No relationships were observed between ecological parameters and CF-CT score, or features of end-stage lung disease. The end-stage CF lung is characterised by a low diversity microbiota, differing within and between individuals. No clear relationship was observed between regional microbiota variation and structural lung damage.

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