Fungal Microbiota in Cystic Fibrosis

Background: The cystic fibrosis (CF) lung microbiota has been characterized in several studies and the observation between loss of bacterial diversity with increasing age and disease progression has been well-described. However, the dynamic relationship between the change in bacterial microbiota over time and increasing fungal colonization in CF with age remains understudied. Little is known about the role of asymptomatic fungal airway colonisation in CF and its impact on lung disease progression and the airway microbiota. Objectives: To longitudinally study the dynamic changes in sputum fungal composition, airway microbiome rarefication and disease progression in CF. Methods: A prospective, single-centre study including adult and paediatric CF patients. Sputum and/or BAL samples were processed for fungal culture (FC) and high-throughput sequencing for bacteria and fungi. Results: 235 respiratory samples were collected from 70 CF patients. Sixty-one percent (n=43) of cohort included paediatric patients aged 0-18 years. The median age at recruitment was 17 years (range 6 months–59 years) with 32 male participants and a median percent predicted FEV1 of 88% (range 26–135%). Sixty percent of CF participants has a least one positive result for Aspergillus fumigatus during the study period, of which 3% were persistently colonised. The majority of patients who were FC naïve (68%) were aged less than 15 years. Fungal culture positivity, advanced disease stage, use of antibiotics and inhaled steroid was significantly associated with a reduced bacterial diversity compared to fungal diversity. Streptococcus was the predominant bacterial taxa in both the FC positive and negative group (24% vs 22% respectively), followed by Pseudomonas (17% vs 19%). Greater abundance of Haemophilus was noted in the FC positive group in comparison to the FC negative group where higher levels of Neisseria were reported. There was a higher abundance of bacterial and fungal rare taxa in the FC negative groups. Both FC groups showed a predominance of Candida and Aspergillus species. Longitudinal analyses showed a steeper decline in bacterial and fungal diversity in CF participants with evidence of persistent fungal colonisation. The most dominant genus across all FC states over time was Streptococcus. Other bacteria that dominated in the FC naïve and transient groups included Veillonella and Nesisseria species in contrast to the FC colonized group which showed greater predominance of Stenotrophomonas and less Veillonella and Neisseria species. A variable pattern of fungal species was noted in the sub-groups naïve or transient for fungi. Aspergillus species was strikingly dominant in CF patients with persistent fungal colonisation. Conclusion: Asymptomatic fungal culture positivity is associated with changes in the bacterial and fungal microbiota. Persistent fungal airway colonisation is associated with a steeper decline in bacterial and fungal diversity over time. Longitudinal differences in bacterial and fungal microbiota were also observed between differing fungal culture states.