227. TEMPORAL DYNAMICS OF GUT FUNGI IN DRUG-NAïVE FIRST-EPISODE SCHIZOPHRENIA PATIENTS DURING ANTIPSYCHOTICS TREATMENT

Abstract Background Bacterial dysbiosis has been demonstrated in patients with schizophrenia (SCZ). However, fewer studies have focused on the role of gut fungi (mycobiota) in SCZ, particularly the temporal changes in fungal populations before and after antipsychotic treatment. Aims & Objectives This study aimed to investigate the differences in gut fungal composition between drug-naïve, first-episode SCZ patients and healthy controls (HCs) and to observe the dynamic changes in gut fungi in SCZ patients during antipsychotic treatment. Method 80 drug-naïve, first-episode SCZ patients and 46 healthy controls (HCs) were recruited. Gut fungal compositions were characterized using 18S ribosomal RNA gene amplicon sequencing. We analyzed fungal composition and abundance alterations at four time points (baseline, 4 weeks, 8 weeks, and >12 weeks) during treatment with antipsychotics (olanzapine, risperidone, aripiprazole, and amisulpride) and assessed changes in fungal networks over time. Results SCZ patients had significantly decreased in α-diversity (Shannon index, p = 0.002; Simpson index, p = 0.002) and β-diversity (p = 0.0077) compared to HCs. After antipsychotic treatment, both α-diversity and β-diversity in SCZ patients exhibited variations over time and gradually approached levels similar to HCs (Shannon index: 4 weeks p = 0.006, 8 weeks p = 0.004, >12 weeks p = 0.32; Simpson index: 4 weeks p = 0.007, 8 weeks p = 0.009, >12 weeks p = 0.35; β-diversity: 4 weeks p = 0.043, 8 weeks p = 0.092, >12 weeks p = 0.66). To detect changes in fungal abundance in SCZ patients after administration of the drug, we used unsupervised classification to identify five fungal clusters; clusters 1, 4, and 5 were significantly more abundant in SCZ patients and decreased to levels similar to HCs during treatment, suggesting an association with antipsychotic treatment rather than the disease itself. Clusters 2 and 3 did not change significantly with drug usage, indicating a possible link to the disease independent of treatment. Certain fungi, including Apiotrichum domesticum, Candida albicans, Cutaneotrichosporon jirovecii, Malassezia globosa, and Xenomyrothecium tongaense, were more abundant in SCZ patients and decreased after treatment, suggesting a disease association. Conversely, fungi such as Colletotrichum truncatum, Rhodotorula diobovata, Septoria cretae, and Stemphylium solani were more abundant in HCs, with their abundance decreasing over time in patients, indicating a potential role in health. Moreover, correlation network analysis revealed fewer fungal associations in SCZ patients than in HCs, which increased after antipsychotic treatment, especially after 12 weeks, suggesting that fungi dysbiosis in SCZ patients. Discussion & Conclusions Our study demonstrated that the gut fungal community in SCZ patients undergoes dynamic changes during antipsychotic treatment. These findings highlight the importance of considering temporal changes in gut mycobiota of microbiota research related to schizophrenia.