Zhang Lan, Pang Xiao-Wei, Zhang Lu-Yang, Zhu Li-Fang, Li Wan-Ning, Chu Yun-Hui, Zhou Luo-Qi, Tian Dai-Shi, Qin Chuan, Chen Lian
Department of Neurology, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic infectious Diseases, Huazhong University of Science and Technology, Wuhan 430030, China.
Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China.
eNeuro. 2025 Sep 4;12(9). doi: 10.1523/ENEURO.0586-24.2025. Print 2025 Sep.
The causal relationship between gut microbiota (GM) and white matter injury and communication remains unclear. We aimed to scrutinize the plausible causal impact of GM on white matter hyperintensities (WMHs), white matter microstructure, white matter connectivity, and multiple neurological diseases via Mendelian randomization study. We identified four WMH-related bacterial taxa, including class , order , family , and genus In addition, three bacterial taxa were discovered that have consistent effect on multiple aspects of white matter microstructure. Furthermore, we found 12 strong associations between genetic liability in GM and white matter connectivity. Among these bacterial taxa, the family demonstrated a protective effect against ischemic stroke (IS). The genus showed protective effect on IS and small vessel stroke while posed a risk effect on neuromyelitis optica spectrum disorder (NMOSD), as well as on aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD). The order and family showed protective effect against cardioembolic stroke, and the genus showed a protective effect on amyotrophic lateral sclerosis. In terms of the mapped genes of statistically significant bacterial taxa, genes such as , , , , , and exhibited a significant causal correlation with the corresponding white matter connectivity. This study demonstrated a genetically predicted causal relationship between GM and WMH, white matter microstructure, white matter connectivity, and multiple neurological diseases, based on GWAS data from mixed-sex cohorts without sex-stratified summary statistics. These findings highlight the potential role of GM in influencing brain structural integrity.
肠道微生物群（GM）与白质损伤及连通性之间的因果关系仍不明确。我们旨在通过孟德尔随机化研究，仔细审查GM对脑白质高信号（WMH）、白质微观结构、白质连通性以及多种神经系统疾病可能产生的因果影响。我们确定了四种与WMH相关的细菌分类群，包括纲 、目 、科 和属 。此外，还发现了三种对白质微观结构的多个方面具有一致影响的细菌分类群。此外，我们发现GM中的遗传易感性与白质连通性之间存在12种强关联。在这些细菌分类群中，科 对缺血性中风（IS）具有保护作用。属 对IS和小血管中风具有保护作用，而对视神经脊髓炎谱系障碍（NMOSD）以及水通道蛋白4免疫球蛋白G阳性视神经脊髓炎谱系障碍（AQP4-IgG+ NMOSD）具有风险作用。目 和科 对心源性栓塞性中风具有保护作用，属 对肌萎缩侧索硬化具有保护作用。就具有统计学意义的细菌分类群的映射基因而言，诸如 、 、 、 、 和 等基因与相应的白质连通性表现出显著的因果相关性。本研究基于来自无性别分层汇总统计的混合性别队列的全基因组关联研究（GWAS）数据，证明了GM与WMH、白质微观结构、白质连通性以及多种神经系统疾病之间存在遗传预测的因果关系。这些发现突出了GM在影响脑结构完整性方面的潜在作用。
