Ling Zongxin, Cheng Yiwen, Liu Xia, Xu Xiaocui, Wu Lingbin, Shao Li, Zhu Zhangcheng, Ding Wenwen, Song Qinghai, Zhao Longyou, Jin Guolin
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Department of Intensive Care Unit, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Front Immunol. 2025 Jul 21;16:1607739. doi: 10.3389/fimmu.2025.1607739. eCollection 2025.
Schizophrenia (SZ) is a severe psychiatric disorder with a complex etiology involving both genetic and environmental factors. Emerging evidence highlights the role of gut microbiome dysbiosis in SZ, yet the fungal component (mycobiota) remains largely unexplored. This study aimed to evaluate the gut mycobiota using internal transcribed spacer 1 (ITS1) amplicon sequencing and assess host immune responses via multiplex immunoassays in 87 elderly SZ patients and 64 age- and gender-matched healthy controls (HCs). We observed significant increases in fungal α-diversity and richness, along with altered β-diversity in SZ patients. Specifically, there was an elevated Basidiomycota/Ascomycota ratio, with enrichment of , , and , coupled with a depletion of . Enterotype analysis revealed a shift from -dominant (E1) to -dominant (E2) communities in SZ. Notably, key fungal species, such as and , were correlated with systemic immune dysfunction. Our receiver operating characteristic (ROC) analysis indicated that these fungal species could effectively distinguish SZ patients from HCs, suggesting their potential as non-invasive biomarkers for SZ diagnosis. In conclusion, this study demonstrates significant alterations in the gut mycobiota and immune dysfunction in elderly SZ patients, suggesting that mycobiota dysbiosis may contribute to SZ pathogenesis through immune modulation, offering new avenues for potential biomarkers and therapeutic interventions.
精神分裂症（SZ）是一种严重的精神疾病，其病因复杂，涉及遗传和环境因素。新出现的证据凸显了肠道微生物群失调在精神分裂症中的作用，但真菌成分（真菌群）在很大程度上仍未得到充分研究。本研究旨在使用内转录间隔区1（ITS1）扩增子测序评估肠道真菌群，并通过多重免疫测定评估87例老年精神分裂症患者和64例年龄和性别匹配的健康对照（HCs）的宿主免疫反应。我们观察到精神分裂症患者的真菌α多样性和丰富度显著增加，同时β多样性也发生了改变。具体而言，担子菌门/子囊菌门的比例升高， 、 和 富集，同时 减少。肠型分析显示，精神分裂症患者的群落从以 为主导（E1）转变为以 为主导（E2）。值得注意的是，关键真菌物种，如 和 ，与全身免疫功能障碍相关。我们的受试者工作特征（ROC）分析表明，这些真菌物种可以有效地区分精神分裂症患者和健康对照，表明它们作为精神分裂症诊断的非侵入性生物标志物的潜力。总之，本研究证明了老年精神分裂症患者肠道真菌群和免疫功能障碍的显著改变，表明真菌群失调可能通过免疫调节导致精神分裂症发病机制，为潜在的生物标志物和治疗干预提供了新途径。
