Zhu Baoyuan, Liang Liqin, Chen Shuhao, Li Hehua, Huang Yuanyuan, Wang Wei, Zhang Heng, Zhou Jing, Xiong Dongsheng, Li Xiaobo, Li Junhao, Ning Yuping, Shi Xuetao, Wu Fengchun, Wu Kai
School of Material Science and Engineering, South China University of Technology, Guangzhou, China.
School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, China.
Transl Psychiatry. 2025 Jul 5;15(1):228. doi: 10.1038/s41398-025-03449-6.
Accumulating evidence has highlighted alterations in the gut microbiome in schizophrenia (SZ); however, the role of multi-kingdom microbiota in SZ remains inadequately understood. In this study, we performed metagenomic sequencing of fecal samples from 36 SZ patients and 55 healthy controls (HC) to profile bacterial, fungal, archaeal, and viral communities, along with functional pathways. We also conducted co-occurrence network analysis to explore the relationships among differential microbial species and metabolic pathways separately. Additionally, we assessed the associations of these differential species and functional pathways with clinical characteristics. Our findings revealed significant differences in species between SZ patients and HC, identifying not only 17 bacterial species, but also 8 fungal, 26 archaeal, and 19 viral species. Functional pathway analysis revealed 21 metabolic pathways significantly altered in SZ patients, including an increase in tryptophan metabolism, while biosynthesis of amino acids was decreased. Network analysis further uncovered more complex inter-kingdom interactions in SZ patients, with specific fungal species appearing exclusively in the SZ network. Importantly, significant associations were observed between microbial species and functional pathways with clinical characteristics, including symptom severity, cognitive function, and clinical biochemical marker. For instance, the abundance of Streptococcus vestibularis was positively correlated with homocysteine levels; the ubiquinone and other terpenoid-quinone biosynthesis was positively correlated with both symptom severity and C-reactive protein. Our findings reveal the intricate microbial dysbiosis present in SZ patients, suggesting multi-kingdom microbial interactions play a crucial role in SZ patients, highlighting promising avenues for potential diagnostic and therapeutic applications.
越来越多的证据表明精神分裂症(SZ)患者的肠道微生物群存在改变;然而,多界微生物群在SZ中的作用仍未得到充分理解。在本研究中,我们对36例SZ患者和55例健康对照(HC)的粪便样本进行了宏基因组测序,以分析细菌、真菌、古菌和病毒群落以及功能通路。我们还进行了共现网络分析,以分别探索差异微生物物种和代谢通路之间的关系。此外,我们评估了这些差异物种和功能通路与临床特征的关联。我们的研究结果显示,SZ患者和HC之间的物种存在显著差异,不仅鉴定出17种细菌物种,还鉴定出8种真菌、26种古菌和19种病毒物种。功能通路分析显示,SZ患者中有21条代谢通路发生了显著改变,包括色氨酸代谢增加,而氨基酸生物合成减少。网络分析进一步发现SZ患者中存在更复杂的跨界相互作用,特定的真菌物种仅出现在SZ网络中。重要的是,观察到微生物物种和功能通路与临床特征之间存在显著关联,包括症状严重程度、认知功能和临床生化指标。例如,前庭链球菌的丰度与同型半胱氨酸水平呈正相关;泛醌和其他萜类醌生物合成与症状严重程度和C反应蛋白均呈正相关。我们的研究结果揭示了SZ患者中存在复杂的微生物失调,表明多界微生物相互作用在SZ患者中起关键作用,为潜在的诊断和治疗应用指明了有前景的方向。
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