The emerging world of the fungal microbiome

Abstract

The study of the fungal microbiota ('mycobiome') is a new and rapidly emerging field that lags behind our understanding of the bacterial microbiome. Every human has fungi as part of their microbiota, but the total number of fungal cells is orders of magnitude smaller than that of the bacterial microbiota. However, the impact of the mycobiome on human health is significant, especially as a reservoir for blooms of pathogenic microbes when the host is compromised and as a potential cofactor in inflammatory diseases and metabolic disorders.

Figure 1

The rare biosphere and the fungal microbiome. (A) Representation of the membership of the microbiome, displayed as a rank abundance curve and illustrating the concept of the ‘rare biosphere’ within the entirety of the microbiome and the relative position of a microbe at 0.01% abundance (asterisk) in this example. In the complex microbial communities of the mucosa, a relatively small number of species dominate, but hundreds to thousands of low abundance species also exist in the communities. At mucosal sites where bacterial abundance can reach >10¹⁰/g, a microbe present at 10⁴/g would be <0.0001% of the cellular content of the community. Microbial diversity in the microbiome is extensive and the large number of low abundance species (or operational taxonomic units, OTUs) in mucosal samples have been described as part of a rare biosphere [2,3]. However, the rare biosphere serves as a reservoir for potentially pathogenic microbes, such as members of the fungal microbiome, which grow out (bloom) and cause disease when the mucosal environment is disturbed. The rare biosphere may also harbor species that have a disproportionate effect (positive or negative) on the dominant members of the microbiome, a potential pathway by which the fungal microbiome may promote chronic disease. (B) Estimated relative cellular abundance of fungi to bacteria in human feces, based upon the MetaHIT metagenomic analysis [1].

Figure 2

Mechanisms by which the fungal microbiome can grow out and cause disease on mucosal surfaces. The fungal microbiome exists on mucosal surfaces in a symbiotic relationship with the host and the bacterial microbiome. Any of the following will promote the outgrowth of fungi on a mucosal surface: disruption of bacteria-mediated colonization resistance by antibiotics; damage to the mucosa by uncontrolled inflammatory responses, physical damage, or chemical-mediated injury; or defects in host defenses/immunity that affect innate immunity or specific facets of adaptive immunity.

Figure 3

Fungal ribosomal gene locus. The most commonly used genetic region used for culture-independent molecular analysis of fungal diversity. Both clone library/sanger sequencing and pyrosequencing have been used to map and catalogue this region. High-throughput pyrosequencing has been used for amplicon libraries generated through pan-fungal internal transcribed spacer regions (ITS) primers that span the region between the 3′ end of the 18S gene, includes the entire 5S gene, and ends in the 5′ region of the 28S gene [9]. This region has been previously demonstrated to amplify a wide range of medically relevant fungi by PCR and pyrosequencing [–11].

Figure 4

Hypothetical representation of the effect of the presence and absence of a fungal outgrowth that modulates bacterial community reassembly. Reassembly of the bacterial microbiome after antibiotic therapy is an ordered process (T_A→T₁→T₂→T₀). Emerging evidence suggests that reassembly may be impacted by the bloom of specific fungal species when colonization resistance is destroyed. This figure provides an illustration of an ecological modeling (ordination) of such a process, in which the bacterial community structure undergoes a different reassembly process (T_A→T_1f→T_2f→T₀) in the presence of a fungal bloom. In this example, the differences in bacterial community structure (membership, richness, and evenness) between the T_A→T₁→T₂→T₀ path and the T_A→T_1f→T_2f→T₀ path could manifest as secondary changes in microbiome-mediated physiologic processes such as immune regulation or metabolism. Abbreviation: T, timepoint.