Characteristics of gut mycobiome in gout patients and their clinical correlation

Objective‍ ‍To compare the gut fungal composition between gout patients and healthy individuals through high-throughput sequencing of ribosomal DNA internal transcribed spacer 1 (ITS1). Methods‍ ‍Gout patients and healthy volunteers who visited our hospital from January 2023 to December 2024 were enrolled in this study. Then based on established medical guidelines, the gout patients were categorized into 3 groups: Group H (asymptomatic hyperuricemia, n=14), Group G (acute gouty arthritis, n=14), and Group I (intercritical period of gouty arthritis, n=15), and the healthy individuals were assigned into Group N (n=9). Fecal samples were collected from all the participants to undergo ITS1 sequencing analysis. The differences in diversity and composition of gut mycobiome, and FunGuild-derived fungal functions and nutritional status were compared among the 4 groups, and the correlation between the gut mycobiome and clinical indicators was analyzed. Results‍ ‍There were no significant differences in baseline features such as gender, age, glomerular filtration rate (GFR), and levels of serum creatinine (SCr) and serum urea among Group N and other gout groups, but obvious differences were observed in body mass index (BMI), erythrocyte sedimentation rate, and levels of C-reactive protein (CRP), serum uric acid (SUA), and IL-1β and IL-6 (P<0.05). In terms of gut fungal diversity, ITS1 analysis showed there were no statistical differences in α-diversity or the principal coordinate analysis (PCoA) of β-diversity among the groups. However, as gout progressed, significant changes were observed in β-diversity indices, indicating a shift in the gut fungal community composition with disease advancement (P<0.05). The phyla Ascomycota, Basidiomycota, and Mucoromycotina were the dominant fungal phyla in all groups. Compared with the other 3 gout groups, the abundance of Pichia was significantly increased in Group N (P<0.05), that of Saccharomyces was in Group H (P<0.05), and that of Starmerella was in Group G (P<0.05). Correlation analysis between the gut mycobiome and clinical indices indicated that the relative abundance of Starmerella was significantly positively correlated with IL-1β (P<0.01) and IL-6 (P<0.05).The relative abundance of Pichia was significantly positively correlated with IL-1β and IL-6 levels (P<0.05), and negatively correlated with serum urea level (P<0.05), and the relative abundance of Saccharomyces was negatively correlated with IL-1β and IL-6 levels (P<0.05). Conclusion‍ ‍There exist significant alterations in both the diversity and composition of gut fungi among patients with gout at various stages. Notably, the fluctuations in the relative abundance of Starmerella, Pichia and Saccharomyces appear to correlate with key clinical indicators.