Respiratory mycobiome and suggestion of inter-kingdom network during acute pulmonary exacerbation in cystic fibrosis

Perrine Soret (1, 2) , Louise-Eva Vandenborght (3, 4) , Florence Francis (1) , Noémie Coron (3, 5, 6) , Raphaël Enaud (3, 6) , Marta Avalos (1, 2) , Thierry Schaeverbeke (6) , Patrick Berger (3, 6) , Michael Fayon (3, 7, 6) , Rodolphe Thiébaut (1, 2) , Laurence Delhaes (3, 7, 8, 9, 6)

1 BPH - Bordeaux population health
2 SISTM - Statistics In System biology and Translational Medicine
3 CRCTB - Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux]
4 Genoscreen [Lille]
5 CHU Bordeaux
6 FHU ACRONIM - Aquitaine’s Care and Research organisation for inflammatory and Immune-Mediated diseases [CHU Bordeaux]
7 CIC Bordeaux
8 Université de Lille
9 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]

Lung infections play a critical role in cystic fibrosis (CF) pathogenesis. CF respiratory tract is now considered to be a polymicrobial niche and advances in high-throughput sequencing allowed to analyze its microbiota and mycobiota. However, no NGS studies until now have characterized both communities during CF pulmonary exacerbation (CFPE). Thirty-three sputa isolated from patients with and without CFPE were used for metagenomic high-throughput sequencing targeting 16S and ITS2 regions of bacterial and fungal rRNA. We built inter-kingdom network and adapted Phy-Lasso method to highlight correlations in compositional data. The decline in respiratory function was associated with a decrease in bacterial diversity. The inter-kingdom network revealed three main clusters organized around Aspergillus, Candida, and Scedosporium genera. Using Phy-Lasso method, we identified Aspergillus and Malassezia as relevantly associated with CFPE, and Scedosporium plus Pseudomonas with a decline in lung function. We corroborated in vitro the cross-domain interactions between Aspergillus and Streptococcus predicted by the correlation network. For the first time, we included documented mycobiome data into a version of the ecological Climax/Attack model that opens new lines of thoughts about the physiopathology of CF lung disease and future perspectives to improve its therapeutic management.

Domaines: Pneumologie et système respiratoire; Mycologie

Perrine Soret, Louise-Eva Vandenborght, Florence Francis, Noémie Coron, Raphaël Enaud, et al.. Respiratory mycobiome and suggestion of inter-kingdom network during acute pulmonary exacerbation in cystic fibrosis. Scientific Reports, 2020, 10 (1), pp.3589. ⟨10.1038/s41598-020-60015-4⟩. ⟨inserm-02497484⟩