Clinical Efficacy and Safety of Hypericin‐Mediated Photodynamic Therapy for Oral Candida albicans Infections

Objective This study evaluated the efficacy and safety of hypericin‐mediated photodynamic therapy (PDT) for oral Candida albicans ( C. albicans ) infections and explores how C. albicans reduction mediates clinical improvement. Methods A total of 107 patients (March 2023–March 2025) were assigned to a control group ( n = 51, conventional antifungal therapy) or a study group ( n = 57, hypericin + PDT). Post‐treatment assessments included oral microbiota structure, α‐diversity (Chao1, Shannon, Simpson), community differences (via PCoA and hierarchical clustering), and a mediation model to test C. albicans ' role in lesion improvement. Results Chao1 (species richness) showed no significant difference, but the study group had lower Shannon/Simpson (microbial diversity). Opportunistic pathogens (e.g., C. albicans , Fusobacterium) decreased, while beneficial bacteria (e.g., Lactobacillus) increased. PCoA/clustering confirmed distinct community structures. C. albicans reduction mediated 53.1% of lesion size reduction (indirect effect = −2.656; 95% CI: 0.178–5.755). Conclusion Hypericin + PDT effectively treats oral C. albicans infections safely. C. albicans is the core mediator for lesion area reduction, providing a basis for targeted clinical therapy.