Metabolomic profiling reveals alterations in Candida pathophysiology and host interactions during primary oral candidiasis and following antifungal treatment.

Comparative metabolomics may shed light on host immunity and biology in oral candidiasis (oral thrush). Untargeted metabolomic analyses were performed on oral rinses collected from 26 primary oral candidiasis patients (OT), 12 patients after antifungal treatment (AT), and 12 unaffected individuals (C). Host immune modulation metabolites against oral candidiasis, Candida virulence and antifungal properties were identified. The upregulation of C17 sphinganine, L-leucine, monoacylglycerol, phosphatidylethanolamine, and spermine, in OT and AT groups, highlights the role of host immunity in Candida clearance. The altered sphingolipid levels suggest disrupted membrane integrity and immune function, while dysregulated amino acid, purine, and glutathione metabolism reflect oxidative stress and inflammation. Antifungal metabolites, specifically dichloroacetate, 1-monopalmitin, and undecane-2-one, were significantly upregulated in the OT group; conversely, fatty acids (palmitic amide, linoleamide, stearamide, and pentadecanal) were downregulated. Metabolomic similarities between oral candidiasis and xerostomia were evident, with shared markers such as L-valine, L-leucine, D-proline and 4-hydroxyphenylpyruvic acid. Increases in lipid metabolites, carboxylic acids, and amino acids, particularly L-leucine and hypoxanthine in patients upon resolution of oral candidiasis following antifungal treatment suggests fungal clearance, immune activation and recovery from oxidative stress. Some metabolites identified in oral candidiasis patients have reported roles in oral carcinogenesis, however, the findings remain observational and warrant further validation. Our results demonstrate that oral candidiasis is associated with distinct metabolomic alterations compared with healthy controls, and that antifungal therapy reshapes the oral metabolic profiles via complex host-microbiome-fungal metabolic pathways. The identification of oral candidiasis-associated metabolites also highlights their potential as non-invasive biomarkers and therapeutic targets for oral healthcare.