The fungal pathogen and mycobiota diversity in respiratory samples from children with cystic fibrosis
Background: The prevalence of fungi in cystic fibrosis (CF) lung infections is poorly understood and studies have focused on adult patients. We investigated the fungal (mycobiota) diversity in children with CF using brochoalveolar lavage (BAL) and induced sputum (IS) samples to capture multiple lung niches.   Methods: Sequencing of the fungal ITS2 region and molecular mycobiota diversity analysis was performed on 25 matched sets of BAL-IS samples from 23 children collected as part of the CF-SpIT study (UKCRN14615; ISRCTNR12473810).   Results: Aspergillus?and?Candida?were detected in all samples and were the most abundant and prevalent genera, followed by?Dipodascus, Lecanicillium and Simplicillium. The presumptive CF pathogens Exophiala, Lomentospora and Scedosporium were identified at variable abundances in 100%, 64%, and 24% of sample sets, respectively. Fungal pathogens observed at high relative abundance (=40%) were not accurately diagnosed by routine culture microbiology in over 50% of the cohort. The fungal communities captured by BAL and IS samples were similar in diversity and composition, with exception to C. albicans?being significantly increased in IS samples. The respiratory mycobiota varied greatly between individuals, with only 13 of 25 sample sets containing a dominant fungal taxon. In 11/25 BAL sample sets, airway compartmentalisation was observed with diverse mycobiota detected from different lobes of the lung.   Conclusions: The paediatric mycobiome is diverse, complex and inadequately diagnosed by conventional microbiology. Overlapping fungal communities were identified in BAL and IS samples, showing that IS can capture fungal genera associated with the lower airway. Compartmentalisation of the lower airway presents difficulties for consistent mycobiota sampling.