Metagenomic profiling reveals distinct gut mycobiome signatures in patients with gout

Gout is a common inflammatory arthritis driven by hyperuricemia and monosodium urate crystal deposition. Although gut bacterial dysbiosis has been implicated in gout, the role of the gut mycobiome remains poorly understood. Here, we reanalyzed publicly available fecal metagenomic data from 307 samples, including healthy controls, untreated gout patients, longitudinal post-treatment samples, and an independent validation cohort, to characterize gout-associated fungal alterations and their relationships with bacterial communities and clinical indicators. Gut fungal profiles were generated using a customized fungal reference database. Differential taxa were identified using Microbiome Multivariable Association with Linear Models 2 (MaAsLin2) after adjustment for available covariates. Gout patients showed altered fungal community structure without marked changes in alpha diversity, suggesting taxon-specific rather than global fungal dysbiosis. Four differential fungal genera and six candidate fungal species were identified, including control-enriched Cutaneotrichosporon c141, Cyberlindnera jadinii c124, and Phialophora verrucosa c161, and gout-enriched Aspergillus terreus c60, Pichia fermentans c90, and Torulaspora delbrueckii c85. Longitudinal analysis indicated partial and heterogeneous remodeling of fungal signatures during treatment. Procrustes and cross-kingdom microbial–clinical network analyses suggested that fungal alterations were associated with bacterial community structure and clinical indicators related to renal function and inflammation. Genome mining further revealed distinct predicted biosynthetic gene cluster profiles among candidate fungal biomarkers. Random forest models showed that fungal features alone had limited classification performance, but provided complementary information when integrated with bacterial signatures. Overall, this study highlights specific gut fungal alterations associated with gout and suggests that fungi may represent an overlooked component of multi-kingdom microbial dysbiosis. These findings are exploratory and require validation in larger controlled cohorts and functional studies.