Salivary Mycobiome and Metabolomic Profiles in HIV-Infected Men Who Have Sex with Men: An Exploratory Study

To investigate alterations in the oral salivary mycobiome and metabolite profiles of men who have sex with men (MSM) with human immunodeficiency virus (HIV) infection. A total of 36 MSM were enrolled, including individuals with mid-stage HIV infection (HIV, n = 14), patients with acquired immunodeficiency syndrome (AIDS, n = 8), and HIV-negative controls (HIV_neg, n = 14). Saliva samples were analyzed using internal transcribed spacer (ITS) sequencing and untargeted metabolomics based on liquid chromatography-mass spectrometry (LC-MS). Fungal mycobiome analysis revealed that both HIV and AIDS groups exhibited a declining trend in alpha diversity, with significantly reduced Shannon index (HIV vs. HIV_neg: P < 0.05; AIDS vs. HIV_neg: P < 0.01). Candida abundance was significantly increased in HIV (P = 0.003) and AIDS (P < 0.001), with good discriminatory performance. Metabolomic analysis revealed that intergroup differences were primarily enriched in lipids and their derivatives, amino acids and related metabolites. Metabolites were generally upregulated in HIV but declined subsequently in AIDS. Pathway enrichment indicated that HIV was predominantly enriched in immune regulation, inflammatory signaling, and virus infection-related pathways, while AIDS was enriched in pathways linked to opportunistic infections and metabolic alterations. Integrated analysis demonstrated that Candida correlated positively with tyramine, histamine, 5-hydroxyindoleacetic acid, and kynurenic acid, and negatively with glycerol 3-phosphate and 5-acetamidovalerate. These results indicate that HIV infection induces significant alterations in the salivary mycobiome and metabolic landscape. The abundance of Candida and its associated metabolites may serve as potential biomarkers, providing insights for early detection and intervention of HIV/AIDS-related fungal infections.