Gut mycobiota dysbiosis and systemic immune dysfunction in Chinese schizophrenia patients with metabolic syndrome

While bacterial dysbiosis has been extensively studied in schizophrenia with metabolic syndrome (SZ-MetS), the role of gut mycobiota in this comorbidity remains unclear. This study represents the first comprehensive investigation of fungal communities in SZ-MetS patients (n=109) versus healthy controls (HCs, n=101) using ITS1 sequencing and multi-parameter immune profiling. Although global mycobiota structure showed no significant differences, compositional analyses revealed profound taxonomic shifts: pathobionts (<i>Trichosporon asahii</i>, <i>Candida albicans</i>, <i>Lodderomyces elongisporus</i>) were enriched, while putative beneficial species (<i>Saccharomyces cerevisiae</i>, <i>Pleurotus ostreatus</i>) were reduced in patients. Enterotyping identified two mycobiota clusters (<i>Candida</i>-dominant vs <i>Aspergillus</i>-dominant), though their distribution was similar between groups. Notably, machine learning revealed a six-species fungal signature with strong diagnostic potential (AUC = 0.86). Species-specific immune correlations were also observed: inflammatory cytokines such as IL-6 and MIP-1α were positively associated with <i>Ustilago esculenta</i> and <i>Trichosporon asahii</i>, but negatively correlated with <i>Saccharomyces cerevisiae</i>. Furthermore, fungal abundances were differentially correlated with metabolic and psychiatric parameters, with <i>Lodderomyces</i> linked to elevated triglycerides and <i>S. cerevisiae</i> associated with reduced symptom severity. These findings reveal that while overall fungal community structure is preserved, SZ-MetS exhibits distinct mycobiota alterations that interact with host immunity and clinical manifestations, suggesting fungi may contribute to the SZ-MetS vicious cycle through taxon-specific mechanisms.