Ling Zongxin, Cheng Yiwen, Lan Zhiyong, Liu Xia, Zhu Zhangcheng, Ding Wenwen, Xu Xiaocui, Yu Pian, Xu Xiaoxun, Shao Li, Song Qinghai, Liao Rongxian
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Yuhang Institute for Collaborative Innovation and Translational Research in Life Sciences and Technology, Hangzhou, Zhejiang, China.
Front Immunol. 2025 Sep 3;16:1652633. doi: 10.3389/fimmu.2025.1652633. eCollection 2025.
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 (, , ) were enriched, while putative beneficial species (, ) were reduced in patients. Enterotyping identified two mycobiota clusters (-dominant vs -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 and , but negatively correlated with . Furthermore, fungal abundances were differentially correlated with metabolic and psychiatric parameters, with linked to elevated triglycerides and 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.
虽然在伴有代谢综合征的精神分裂症（SZ-MetS）中，肠道细菌失调已得到广泛研究，但肠道真菌群落在这种共病中的作用仍不清楚。本研究首次使用ITS1测序和多参数免疫分析，对SZ-MetS患者（n = 109）与健康对照者（HCs，n = 101）的真菌群落进行了全面调查。尽管整体真菌群结构没有显著差异，但成分分析揭示了深刻的分类学变化：致病共生菌（、、）富集，而假定的有益物种（、）在患者中减少。肠型分析确定了两个真菌群落簇（-优势型与-优势型），尽管它们在两组之间的分布相似。值得注意的是，机器学习揭示了一种具有强大诊断潜力的六种真菌特征（AUC = 0.86）。还观察到物种特异性免疫相关性：IL-6和MIP-1α等炎性细胞因子与和呈正相关，但与呈负相关。此外，真菌丰度与代谢和精神参数存在差异相关，与甘油三酯升高有关，与症状严重程度降低有关。这些发现表明，虽然整体真菌群落结构得以保留，但SZ-MetS表现出与宿主免疫和临床表现相互作用的独特真菌群落改变，提示真菌可能通过特定分类群机制促成SZ-MetS的恶性循环。
