Distinct community structures of the fungal microbiome and respiratory health in adults with cystic fibrosis

Background: The respiratory tract fungal microbiome in cystic fibrosis (CF) has been understudied despite increasing recognition of fungal pathogens in CF lung disease. We sought to better understand the fungal communities in adults with CF, and to define relationships between fungal profiles and clinical characteristics.

Methods: We enrolled 66 adults with CF and collected expectorated sputum, spirometry, Cystic Fibrosis Questionnaire-revised, and clinical data. Fungi were molecularly profiled by sequencing of the internal transcribed spacer (ITS) region. Total fungal abundance was measured by quantitative PCR. Relative abundance and qPCR-corrected abundances were determined. Selective fungus culture identified cultivable fungi. Alpha diversity and beta diversity were measured and relationships with clinical parameters were interrogated.

Results: Median age was 29 years and median FEV₁ percent predicted 58%. Members of the Candida genus were the most frequent dominant taxa in CF sputum. Apiotrichum, Trichosporon, Saccharomyces cerevisiae, and Scedosporium were present in high relative abundance in few samples; whereas, Aspergillus species were detected at low levels. Higher FEV₁% predicted and CFTR modulator use were associated with greater alpha-diversity. Chronic azithromycin use was associated with lower alpha-diversity. Patients with acute pulmonary had distinct fungal community composition compared to clinically stable subjects. Differing yeast species were mainly responsible for the community differences.

Conclusion: The respiratory tract fungal microbiome in adults with CF is associated with lung function, pulmonary exacerbation status, macrolide use, and CFTR modulator use. Future work to better understand fungal diversity in the CF airway and its impact on lung health is necessary.