Oral microbiota, cytokines, and schizophrenia and bipolar disorder: a mediation mendelian randomization study.

OBJECTIVES: Schizophrenia and bipolar disorder have overlapping acute-phase symptoms and unclear etiologies. Recent studies suggest links between oral microbiota, cytokines, and these disorders, but causality is uncertain. This study aims to explore causal relationships using two-sample Mendelian randomization (MR) and mediation analysis. METHODS: First, MR was used to analyze the causal relationship between oral microbiota, cytokines and schizophrenia, bipolar disorder. Second, MR was used to analyze the causal relationship between the oral microbiota associated with these two disorders and the cytokines associated with these two disorders. Finally, mediation analyses were performed to calculate mediation effect values. RESULTS: 48 tongue microbiota, 30 salivary microbiota were causally associated with schizophrenia. 46 tongue microbiota, 41 salivary microbiota were causally associated with bipolar disorder. 7 cytokines were causally associated with schizophrenia. 3 cytokines were causally associated with bipolar disorder. Delta/Notch-like Epidermal Growth Factor-Related Receptor (DNER), Interleukin-6 (IL-6), Stem cell factor (SCF) are mediators between tongue microbiota and schizophrenia. CD40L receptor, Interleukin-7 (IL-7), Vascular endothelial growth factor A (VEGFA) are mediators between salivary microbiota and schizophrenia. Osteoprotegerin (OPG) is a mediator between tongue microbiota and bipolar disorder. TNF-Related Apoptosis-Inducing Ligand (TRAIL) is a mediator between salivary microbiota and bipolar disorder. CONCLUSION: This study systematically discussed the causal relationship between oral microbiota, cytokines and schizophrenia, bipolar disorder. DNER, IL-6, SCF, CD40L receptor, IL-7 and VEGFA are mediators between oral microbiota and schizophrenia, OPG and TRAIL are mediators between oral microbiota and bipolar disorder. This provides new ideas on the pathogenesis and diagnosis of schizophrenia and bipolar disorder.