The Mycobiome in Health and Disease: Emerging Concepts, Methodologies and Challenges

Abstract

Fungal disease is an increasingly recognised global clinical challenge associated with high mortality. Early diagnosis of fungal infection remains problematic due to the poor sensitivity and specificity of current diagnostic modalities. Advances in sequencing technologies hold promise in addressing these shortcomings and for improved fungal detection and identification. To translate such emerging approaches into mainstream clinical care will require refinement of current sequencing and analytical platforms, ensuring standardisation and consistency through robust clinical benchmarking and its validation across a range of patient populations. In this state-of-the-art review, we discuss current diagnostic and therapeutic challenges associated with fungal disease and provide key examples where the application of sequencing technologies has potential diagnostic application in assessing the human 'mycobiome'. We assess how ready access to fungal sequencing may be exploited in broadening our insight into host-fungal interaction, providing scope for clinical diagnostics and the translation of emerging mycobiome research into clinical practice.

Keywords: Bioinformatics; Clinical; ITS sequencing; Metagenomics; Mycobiome.

Fig. 1

Overview of the mycobiome in healthy and diseased states. Purple arrow: cross-talk between lung and gut; grey arrow: dysbiosis. COPD: chronic obstructive pulmonary disease; HIV: human immunodeficiency virus; IBD: inflammatory bowel disease; IBS: irritable bowel syndrome; down arrow: decreased abundance

Fig. 2

Diagram summarising the key challenges in mycobiome sequencing and analysis. PCR: polymerase chain reaction, rRNA: ribosomal ribonucleic acid, ITS: internal transcribed spacer, DNA: deoxyribonucleic acid, OTU: operational taxonomic unit