Metagenomics Applied to the Respiratory Mycobiome in Cystic Fibrosis

Abstract

Cystic fibrosis (CF) is a genetic disorder characterized by chronic microbial colonization and inflammation of the respiratory tract (RT), leading to pulmonary exacerbation (PEx) and lung damage. Although the lung bacterial microbiota has been extensively studied, the mycobiome remains understudied. However, its importance as a contributor to CF pathophysiology has been highlighted. The objective of this review is to provide an overview of the current state of knowledge regarding the mycobiome, as described through NGS-based studies, in patients with CF (pwCF).Several studies have demonstrated that the mycobiome in CF lungs is a dynamic entity, exhibiting a lower diversity and abundance than the bacterial microbiome. Nevertheless, the progression of lung damage is associated with a decrease in fungal and bacterial diversity. The core mycobiome of the RT in pwCFs is mainly composed of yeasts (Candida spp., Malassezia spp.) and molds with lower abundance. Some fungi (Aspergillus, Scedosporium/Pseudallescheria) have been demonstrated to play a role in PEx, while the involvement of others (Candida, Pneumocystis) remains uncertain. The "climax attack" ecological model has been proposed to explain the complexity and interplay of microbial populations in the RT, leading to PEx and lung damage. NGS-based studies also enable the detection of intra- and interkingdom correlations between fungi and bacteria. Further studies are required to ascertain the biological and pathophysiological relevance of these correlations. Finally, with the recent advent of CFTR modulators, our understanding of the pulmonary microbiome and mycobiome in pwCFs is about to change.

Keywords: Cystic fibrosis mycobiome; Fungi; Next-generation sequencing.

Fig. 1

Methods used to study the airway mycobiome in CF patients. Figure adapted from Thornton et al. J Pediatric Infect Dis Soc. 2022 [15] and created with BioRender.com. Abbreviations: ASV amplicon sequence variant; NGS next-generation sequencing; OTU operational taxonomic unit; TA-NGS targeted-amplicon NGS; SMg shotgun metagenomics

Fig. 2

Airway-specific microenvironment in patients with CF. The different specificities of the CF airway microenvironment favor chronic colonization with adapted microorganisms, allowing possible intra- and interkingdom interactions (through biofilm formation and molecular interactions) and leading to repeated pulmonary exacerbations (PEx). Its association with persistent inflammation leads to lung damage and respiratory failure. Abbreviations: Mφ: macrophage; Neut: neutrophil. Adapted from Ubags and Marsland, Eur Respir J. 2017 [31]. The figure was created with BioRender.com

Fig. 3

The “Climax-Attack” model for CF airways. The “Climax-Attack model” is an ecological model adapted to explain the progressive loss of microbial diversity and the replacement of pioneer communities by adapted communities to CF airways. The figure was adapted from the articles of Quinn et al. npj Biofilms Microbiomes. 2016; Soret et al. Sci Rep. 2020; Conrad et al. Am J Respir Cell Mol Biol 2013 [15, 89, 90] and created, in part, with BioRender.com