Oral Fungal Infections: Past, Present, and Future

Oral fungal infections have afflicted humans for millennia. Hippocrates (ca. 460-370 BCE) described two cases of oral aphthae associated with severe underlying diseases that could well have been oral candidiasis. While oral infections caused by other fungi such as cryptococcosis, aspergillosis, mucormycosis, histoplasmosis, blastomycosis, and coccidioidomycosis occur infrequently, oral candidiasis came to the fore during the AIDS epidemic as a sentinel opportunistic infection signaling the transition from HIV infection to AIDS. The incidence of candidiasis in immunocompromised AIDS patients highlighted the importance of host defenses in preventing oral fungal infections. A greater understanding of the nuances of human immune systems has revealed that mucosal immunity in the mouth delivers a unique response to fungal pathogens. Oral fungal infection does not depend solely on the fungus and the host, however, and attention has now focussed on interactions with other members of the oral microbiome. It is evident that there is inter-kingdom signaling that affects microbial pathogenicity. The last decade has seen significant advances in the rapid qualitative and quantitative analysis of oral microbiomes and in the simultaneous quantification of immune cells and cytokines. The time is ripe for the application of machine learning and artificial intelligence to integrate more refined analyses of oral microbiome composition (including fungi, bacteria, archaea, protozoa and viruses—including SARS-CoV-2 that causes COVID-19). This analysis should incorporate the quantification of immune cells, cytokines, and microbial cell signaling molecules with signs of oral fungal infections in order to better diagnose and predict susceptibility to oral fungal disease.