Mining the oral mycobiome: Methods, components, and meaning.

Research on oral fungi has centered on Candida. However, recent internal transcribed spacer (ITS)-based studies revealed a vast number of fungal taxa as potential oral residents. We review DNA-based studies of the oral mycobiome and contrast them with cultivation-based surveys, showing that most genera encountered by cultivation have also been detected molecularly. Some taxa such as Malassezia, however, appear in high prevalence and abundance in molecular studies but have not been cultivated. Important technical and bioinformatic challenges to ITS-based oral mycobiome studies are discussed. These include optimization of sample lysis, variability in length of ITS amplicons, high intra-species ITS sequence variability, high inter-species variability in ITS copy number and challenges in nomenclature and maintenance of curated reference databases. Molecular surveys are powerful first steps to characterize the oral mycobiome but further research is needed to unravel which fungi detected by DNA are true oral residents and what role they play in oral homeostasis.