Abstract
Oral microbial dysbiosis contributes to the development of schizophrenia (SZ). While numerous studies have investigated alterations in the oral bacterial microbiota among SZ patients, investigations into the fungal microbiota, another integral component of the oral microbiota, are scarce. In this cross-sectional study, we enrolled 118 Chinese patients with SZ and 97 age-matched healthy controls (HCs) to evaluate the oral fungal microbiota from tongue coating samples using internal transcribed spacer 1 amplicon sequencing and assess host immunity via multiplex immunoassays. Our findings revealed that SZ patients exhibited reduced fungal richness and significant differences in β-diversity compared to HCs. Within the oral fungal communities, we identified two distinct fungal clusters (mycotypes): Candida and Malassezia, with SZ patients showing increased Malassezia and decreased Candida levels. These key functional oral fungi may serve as potential diagnostic biomarkers for SZ. Furthermore, SZ patients displayed signs of immunological dysfunction, characterized by elevated levels of pro-inflammatory cytokines such as IL-6 and TNF-α, and chemokines including MIP-1α and MCP-1. Importantly, Malassezia mycotype correlated positively with peripheral pro-inflammatory cytokines, while Candida mycotype exhibited a negative correlation with these cytokines. In conclusion, we have demonstrated, for the first time, the presence of altered oral fungal communities and systemic immune dysfunction in Chinese SZ patients compared to HCs, providing novel insights into the potential role of oral fungi as biomarkers and the broader implications for understanding SZ pathogenesis.