Wu Hui, Liu Bingdong, Liu Weiyin Vivian, Wen Zhi, Yang Wenbing, Yang Huaguang, Li Jianbo, Zha Yunfei
Radiology Department, Renmin Hospital of Wuhan University, Wuhan, China.
Psychiatry Department, The First People's Hospital of Kashi, Kashi, China.
Schizophrenia (Heidelb). 2025 Aug 13;11(1):113. doi: 10.1038/s41537-025-00661-7.
Structural and functional brain abnormalities in schizophrenia (SZ) are well-documented, yet the role of the glymphatic system remains largely unexplored. Given emerging evidence linking the microbiome-gut-brain axis to SZ, this study aims to investigate the glymphatic system function in SZ patients using diffusion tensor image analysis along the perivascular space (DTI-ALPS) and to explore its associations with gut microbiota and cognitive performance. Multi-omics data were obtained from a cohort of 87 SZ patients and 70 healthy controls (HCs), including fecal 16S rRNA sequencing, DTI-ALPS index analysis, and cognitive assessments. Correlation and mediation analyses were conducted to explore the relationships among the gut microbiome, DTI-ALPS index, and cognitive performance. Compared to HCs, patients with SZ exhibited significantly lower DTI-ALPS indices in the left, right, and bilateral hemispheres. These indices were positively associated with multiple cognitive domains. In addition, gut microbial dysbiosis was observed in SZ, characterized by a decrease in butyrate-producing bacteria and an increase in pathogenic bacteria. Exploratory analyses further revealed a tripartite link among the key microbial genera, DTI-ALPS indices, and cognitive performance. Notably, the higher abundance of Proteus as well as the lower abundance of Blautia and Faecalibacterium may contribute to poorer cognitive performance, potentially through disruptions in the right DTI-ALPS index. These findings provide novel insights into glymphatic dysfunction in SZ and highlight a potential microbiota-glymphatic-cognition pathway contributing to cognitive impairments.
精神分裂症（SZ）患者大脑的结构和功能异常已有充分记录，但类淋巴系统的作用在很大程度上仍未得到探索。鉴于有新证据将微生物群-肠道-脑轴与精神分裂症联系起来，本研究旨在利用沿血管周围间隙的扩散张量成像分析（DTI-ALPS）来研究精神分裂症患者的类淋巴系统功能，并探讨其与肠道微生物群和认知表现的关联。从87名精神分裂症患者和70名健康对照者（HCs）的队列中获取了多组学数据，包括粪便16S rRNA测序、DTI-ALPS指数分析和认知评估。进行了相关性和中介分析，以探索肠道微生物群、DTI-ALPS指数和认知表现之间的关系。与健康对照者相比，精神分裂症患者在左、右和双侧半球的DTI-ALPS指数显著更低。这些指数与多个认知领域呈正相关。此外，在精神分裂症患者中观察到肠道微生物失调，其特征是产丁酸细菌减少和致病菌增加。探索性分析进一步揭示了关键微生物属、DTI-ALPS指数和认知表现之间的三方联系。值得注意的是，变形杆菌的丰度较高以及布劳特氏菌和粪杆菌的丰度较低可能导致认知表现较差，可能是通过破坏右侧DTI-ALPS指数。这些发现为精神分裂症中的类淋巴功能障碍提供了新的见解，并突出了一条潜在的微生物群-类淋巴-认知途径，该途径导致认知障碍。
