The Human Lung Mycobiome in Chronic Respiratory Disease: Limitations of Methods and Our Current Understanding

Abstract

Purpose of the Review This review summarises the characteristics of the lung mycobiome in patients with chronic respiratory diseases and fungal lung diseases. We have also reviewed the limitations of the current methods in mycobiome studies. Recent Findings Available studies in the impacts of the mycobiome in chronic and fungal lung diseases are scarce and comparison of the available studies is hindered by heterogeneity in the sample sizes, methods and patient selection. Summary The impact of the diversity and composition of the lung mycobiome in chronic and fungal lung diseases is poorly understood. Most studies involve detection of fungi in respiratory samples by culture. However, such methods lack sensitivity and the emergence of next-generation sequencing technologies is an important advance. However, differences in the sequencing methodologies limit study comparisons. Well-designed methodological approaches and large cohort studies are needed to evaluate the impact of the lung mycobiome in respiratory diseases.

The Interactions of Airway Bacterial and Fungal Communities in Clinically Stable Asthma

“…Therefore, future in vivo and vitro experiments are required to confirm the potential mechanism linking these microorganisms of interest with the host. A further limitation is the average of 14.56% unidentified reads of the ITS fungal sequences in our study, indicating the limited sequence availability in fungal databases according to previous studies (Mac Aogain et al, 2018;Weaver et al, 2019). However, most of the fungi that we considered have been effectively classified.…”

“…and Schizophyllum spp. were the dominant fungi in the airways of patients with chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis (CF) and bronchiectasis (Mac Aogain et al, 2018;Weaver et al, 2019).…”

Decades-old studies of fungi associated with mammalian lungs and modern DNA sequencing approaches help define the nature of the lung mycobiome

“…What these early studies missed was the fact that the lung is a microenvironment rich in microorganisms, many of which appear to be adapted to persist there. Similarly, mycobiome studies of humans stand to be informed by studies of wild rodents and other nonhuman mammals, in part because of limitations of sampling and sequencing approaches available for human studies (reviewed by [20]), but also because comparative analyses can help reveal long-term coevolutionary relationships.…”

Factoring in the Complexity of the Cystic Fibrosis Lung to Understand Aspergillus fumigatus and Pseudomonas aeruginosa Interactions

“…Finally, the CF mycobiome has recently emerged as a promising area of research. Previously, the mycobiome was under-recognised due to the low sensitivity of culture-based detection methods, combined with low overall numbers of fungi in the lungs (in comparison to bacteria) and the general perception of these as environmental contaminants [ 75 , 76 ]. In fact, the CF mycobiome is fairly diverse: Aspergillus , Candida , Cladosporium, Penicillium , Scedosporium and Exophiala species have all been identified in CF cohorts [ 77 , 78 ].…”

“…Aspergillus colonisation prevalence in CF patients is between 10–57%, with higher prevalence being associated with increasing age and poorer lung function [ 79 ]. Colonisation occurs when Aspergillus spores germinate and form mycelium at the epithelial surface [ 76 ]. The pathophysiology of progression from colonisation to active pulmonary infection has not yet been fully determined, however, chronic colonisation is a predecessor to pulmonary aspergillosis in compromised hosts [ 106 , 107 ].…”