The lung mycobiome: an emerging field of the human respiratory microbiome

Abstract

The lung microbiome, which is believed to be stable or at least transient in healthy people, is now considered as a poly-microorganism component contributing to disease pathogenesis. Most research studies on the respiratory microbiome have focused on bacteria and their impact on lung health, but there is evidence that other non-bacterial organisms, comprising the viruses (virome) and fungi (mycobiome), are also likely to play an important role in healthy people as well as in patients. In the last few years, the lung mycobiome (previously named the fungal microbiota or microbiome) has drawn closer attention. There is growing evidence that the lung mycobiome has a significant impact on clinical outcome of chronic respiratory diseases (CRD) such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, and bronchiectasis. Thanks to advances in culture independent methods, especially next generation sequencing, a number of fungi not detected by culture methods have been molecularly identified in human lungs. It has been shown that the structure and diversity of the lung mycobiome vary in different populations (healthy and different diseased individuals) which could play a role in CRD. Moreover, the link between lung mycobiome and different biomes of other body sites, especially the gut, has also been unraveled. By interacting with the bacteriome and/or virome, the respiratory mycobiome appears to be a cofactor in inflammation and in the host immune response, and therefore may contribute to the decline of the lung function and the disease progression. In this review, we report the recent limited explorations of the human respiratory mycobiome, and discuss the mycobiome's connections with other local microbial communities, as well as the relationships with the different biomes of other body sites. These studies suggest several outlooks for this understudied emerging field, which will certainly call for a renewal of our understanding of pulmonary diseases.

Keywords: chronic respiratory disease; fungal microbiota; lung; microbiome; mycobiota; respiratory mycobiome.

FIGURE 1

Distribution of fungal classes (in % of relative abundance) in the sputum of healthy individuals (outer ring) and patients with CF (middle ring) and asthma (inner ring), based on published pyrosequencing investigations (Delhaes et al., 2012; van Woerden et al., 2013). The percentages on the legend correspond to each class identified in healthy, CF, and asthma populations (from the outer to inner rings respectively). Reads that were not identified as class level are group at phylum levels (Ascomycota, Basidiomycota). Classes less than 0.1% are not represented in the rings; the class named “Fungi incertae sedis” refers to unclassified fungi.

FIGURE 2

Venn diagram representing the comparison of the respiratory mycobiomes in healthy individuals, and patients with CF or asthma from published studies (Delhaes et al., 2012; van Woerden et al., 2013; Willger et al., 2014). Shared genera are indicated in the overlap regions. The four most frequent species specifically isolated in each population are indicated in the non-overlap regions. Genera and species in red represent known opportunistic pathogens. In healthy people, E. sinecaudum, Vanderwaltozyma polyspora, and Systenostrema alba are Saccharomycetaceae and microsporidia isolated from soil and plants with no known clinical pathogenicity. Cladosporium cladosporioides has been described in cutaneous, subcutaneous, lung, and disseminated infections in immunocompromised patients. In the asthma population, Psathyrella candolleana, Grifola sordulenta, and Termitomyces clypeatus are environnemental Basidomycota. Malassezia pachydermatis is associated with atopic dermatitis. In CF patients, exclusively known opportunistic pathogens are the most frequent: Aspergillus species belonging to the Fumigata section are responsible for allergic disease (ABPA) as well as infection, while the pathogenicity of yeasts (Candida and Malassezia) is still a matter of debate in the context of CF. Among the shared fungal communities: Eremothecium is a filamentous fungus originally isolated from cotton; Pseudotaeniolina members are environmental fungi and occur only rarely in human hosts; Rozella is a widespread genus considered one of the earliest diverging lineages of fungi, isolated from the environment (marine); Protomyces is an Ascomycota phytopathogen; Peniophorella are soil Basidiomycota, of which few species are restricted to the northern hemisphere; Dioszegia are basidiomycetous yeasts found in a wide range of habitats; Phlebiopsis are saprotrophic fungi with a widespread distribution. Cladosporium species are becoming increasingly important opportunistic pathogens, especially in solid organ transplant recipients. Malassezia are members of the human skin flora which are associated with a wide spectrum of clinical manifestations from benign skin conditions (tinea versicolor) to fungemia in the immunocompromised host, or atopic dermatitis.

FIGURE 3

Integrative research based on the lung mycobiome, virome, and bacteriome.