Oral fungal microbiome in gout: composition, cross-kingdom interactions, and effects of intervention

Background Oral fungi, despite their low abundance, may influence microbial interactions, host responses, and disease progression; however, their role in gout remains poorly understood.Materials and methods Between March and December 2024, patients with chronic gouty arthritis (CGA), acute gouty arthritis (AGA), and age- and sex-matched healthy controls (HC) were enrolled. Unstimulated saliva underwent ITS2 sequencing. Analyses included α/β-diversity, differential abundance, and genus-level co-occurrence networks. Cross-kingdom associations were assessed using partial Spearman correlation integrating 16S rRNA data. A subset received lifestyle intervention and urate-lowering therapy with follow-up.Results A total of 76 participants (35 CGA, 17 AGA, 24 HC) were included. Alpha-diversity showed no significant difference, while β-diversity distinguished patients from HC ( P = 0.0018). Ascomycota and Basidiomycota predominated. Alternaria, Eutypella, and Saccharomyces was enriched in CGA. Whereas Eutypella was enriched in AGA. Network analysis revealed progressive loss of fungal–fungal and fungal–bacterial interactions, with strengthened pathogenic fungi–bacteria associations. Follow-up indicated partial restoration of fungal–fungal networks preceding compositional recovery.Conclusion This study provides the first characterization of the oral mycobiome in gout, highlighting weakened microbial connectivity and reinforced pathogen associations. Interventions may restore network integrity before compositional normalization, suggesting the oral mycobiome as a potential target in gout.