The Human Respiratory Microbiome: Implications and Impact

Alicia B. Mitchell, BMedSci (Hons); Allan R. Glanville, MBBS, MD, FRACP


Semin Respir Crit Care Med. 2018;39(2):199-212. 

In This Article

Fungal Studies

Compared with the bacterial component of the lung microbiome, the fungal component termed the "mycobiome" represents a largely understudied area with a fewer than 10 published papers describing the fungal composition of the microbiome using next-generation sequencing (NGS) techniques. Despite the limited data present in this area, there appears to be many parallels between the fungal and bacterial components of the microbiome including the understanding that fungal species are present during health, and that there is significant intrasubject variability in the diversity of species detected.[105] Limited studies have compared fungal and bacterial species in disease states with healthy controls. The most common fungal genera identified in healthy lung samples were Cladosporium, Eurotium, Penicillium, Aspergillus, Candida, and Pneumocystis.[100,106] Similarly to the bacterial component, a large range of fungal species has been found in lung samples since the use of NGS, which are not detectable by culture. Up to 82% of the fungal species detected in sputum samples by sequencing were unable to be cultured. Furthermore, in this group of 55 CF patients, only 27% were found to be positive for fungus when culture-based methods were used, compared with 90% of the cohort being positive by sequencing.[107]

The lung mycobiome has been investigated in CF and COPD, with decreases in fungal diversity being observed. Furthermore, decreased fungal diversity has been associated with lower lung function. It has been suggested that the decreased diversity may be due to outgrowth of a single species, or the loss of rare species as part of overall decreased fungal abundance. In CF, it has been shown that the highest species richness is observed in those with the lowest disease severity scores.[106] Similarly to the observations from the bacterial component of the microbiome, fungal communities also appear to remain stable through antimicrobial therapy and exacerbations.[108,109] There are very limited data regarding the mycobiome in COPD; however, two studies have shown Aspergillus[110] and Pneumocystis[111] to be highly represented species within BAL samples from patients with COPD. How these interact with other fungal species and other bacterial members of the microbiome is yet to be elucidated.

Many aspects impact the microbiome in transplant, including donor transmission, structural changes within the lungs and immunosuppression. However, there is still limited information regarding how these factors impact the mycobiome. The fungal aspect of the microbiome has been characterized in a small set of lung transplant patients showing that in general, there is decreased fungal abundance and diversity compared with healthy controls. Charlson et al characterized the lung mycobiome in 21 patients following lung transplantation, and found that in many cases, it was largely dominated by Candida species which were also found in the oropharyngeal wash of these subjects. In two individuals, high levels of Aspergillus were detected; however, these were largely absent in the oropharyngeal wash samples. Furthermore, Cryptococcus was observed in the BAL samples of six patients at relatively low abundance.[100] Indication for transplant also appears to have an effect. Individuals transplanted for CF showed the lowest species richness.[100]

Certain members of the mycobiome may be associated with negative outcomes post-transplant. Colonization with Aspergillus has been shown to be strongly associated with development of BOS and increased BOS-related mortality using Cox-regression analyses.[112] Willner et al demonstrated that Aspergillus species were decreased in transplant patients who had Pseudomonas-dominated microbiomes, which was shown to be negatively correlated with the development of BOS.[81] Therefore, further characterization of the mycobiome is necessary to determine the contribution of members to negative outcomes post lung transplantation. This may contribute to long-term treatment strategies in microbiome manipulation as a way of mitigating the development and progression of BOS.