The Fungal and Bacterial Microbiome in Cystic Fibrosis (FABB CF): Changes in the Cystic Fibrosis Airway Mycobiome Over Time and its Link with Bacterial Species Rarefication

Background: The significance of airway colonisation with Aspergillus fumigatus in CF lung disease remains uncertain. Bacterial diversity decreases with age in CF, whilst fungal airway colonisation increases. The cause and effect of these findings are not well understood in the pre-modulated CF airway microbiome.

Aims: To longitudinally study the dynamic changes in sputum fungal composition, airway microbiome rarefication, airway inflammatory markers and disease progression in CF.

Methods A prospective, single-centre longitudinal study over a six-year period, including paediatric and adult CF patients. Sputum and/or BAL samples processed for fungal culture (FC), bacterial and fungal quantitative PCR, high-throughput sequencing and airway inflammatory biomarkers. Age-matched paediatric disease-control participants were also recruited.

Results Seventy patients provided 235 respiratory samples. Median age at recruitment was 17 years (range 0.5–59 years) with a median percent predicted FEV1 of 88% (range 26–135%). 60% of participants were FC positive, of which 3% were persistently colonised. 68% of the FC naïve group were aged <15 years. FC positivity was independently associated with reduced bacterial diversity. Streptococcus and Pseudomonas were the predominant taxa across both FC groups. Rare bacterial and fungal taxa were more abundant within the FC negative cohort. Participants with persistent fungal airway colonisation displayed differences in bacterial and fungal community structure, and demonstrated a steeper decline in fungal diversity over time. This cohort also demonstrated a predominance of Candida parapsilosis, C. albicans and A. fumigatus. There was no significant difference between airway biomarkers in relation to fungal culture positivity.

Conclusion Chronic Aspergillus fumigatus airway colonisation is associated with a change in bacterial and fungal community structure and diversity in CF. Further comparative studies are needed to understand the impact of fungal airway colonisation on the modulated CF airway microbiome.