高水平的血浆Neurturin部分介导Ruminococcus丰度降低对多发性硬化症的保护作用：一项孟德尔随机化研究
High Levels of Plasma Neurturin Partially Mediate the Protective Effect of Reduced Ruminococcus2 Abundance on Multiple Sclerosis: A Mendelian Randomization Study.
摘要(中文译文)
遗传学证据表明肠-脑轴参与神经退行性疾病（NDDs）的发生。肠道微生物群改变和炎症是关键病理生理因素。阐明遗传基础及细胞因子的作用可为肠道微生物组成与神经退行性变之间的关联机制提供见解。利用五项大型全基因组关联研究（GWAS）的汇总统计数据，涵盖阿尔茨海默病、帕金森病、路易体痴呆、多发性硬化和肌萎缩侧索硬化，采用双向两样本孟德尔随机化（MR）方法检验上述关联。进一步采用两步法多变量孟德尔随机化方法，纳入91种细胞因子的数据以探索潜在中介因素。研究揭示了肠道微生物群与NDDs之间存在18项正向效应和17项负向效应，细胞因子与NDDs之间存在10项正向效应和10项负向效应。值得注意的是，中介分析识别出一条因果通路，有证据表明血浆神经营养因子（neurturin）水平部分中介了Ruminococcus2属与多发性硬化之间的关联，中介比例为19.19%（OR = 1.038，95% CI = 1.001-1.086，P = 0.044）。未检测到多效性或异质性。这些MR研究结果为NDDs中由遗传学支撑的肠-免疫-脑网络提供了有力证据，细胞因子作为中间介质。双向效应凸显了疾病特异性微生物特征和炎症背景。多发性硬化中的Ruminococcus2-神经营养因子通路可能提供机制特异性，与神经营养及抗炎信号通路相一致。本研究强调了肠道微生物群改变在NDDs中的重要性，并探讨了炎症的部分中介作用。研究结果提示了个性化神经退行性疾病预防策略的潜在靶点。
Abstract
Genetic evidence implicates the contribution of the gut-brain axis to neurodegenerative diseases (NDDs). Alterations in gut microbiota and inflammation are key pathophysiological contributors. Elucidating the genetic basis and the role of cytokines can provide insights into mechanisms linking gut microbial composition to neurodegeneration. Using aggregated statistics from five large-scale Genome-Wide Association Studies (GWAS) on Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, multiple sclerosis, and amyotrophic lateral sclerosis, bidirectional two-sample Mendelian Randomization (MR) was used to examine the associations. A two-step multivariable Mendelian randomization approach incorporates data from 91 cytokines to explore potential mediators. The study reveals 18 positive and 17 negative effects between gut microbiota and NDDs, as well as 10 positive and 10 negative effects between cytokines and NDDs. Remarkably, mediation analysis identified a causal pathway, with evidence that plasma neurturin levels partially mediate the association from genus Ruminococcus2 to multiple sclerosis, with a mediation proportion of 19.19% (OR = 1.038, 95% CI = 1.001-1.086, P = 0.044). No pleiotropy or heterogeneity was detected. These MR findings provide compelling evidence for a genetically anchored gutimmune-brain network in NDDs, with cytokines as intermediates. Bidirectional effects highlight disease-specific microbial signatures and inflammatory contexts. The Ruminococcus2-neurturin pathway in multiple sclerosis may offer mechanistic specificity, aligning with neurotrophic and anti-inflammatory signaling pathways. This study emphasizes the importance of gut microbiota alterations in NDDs and explores inflammation's partial intermediary role. The findings suggest potential targets for personalized neurodegeneration prevention strategies.
如何引用
AMA
Yalin Liu, Jiaoyan Yang, Jingyang Su, Liying Hao. High Levels of Plasma Neurturin Partially Mediate the Protective Effect of Reduced Ruminococcus2 Abundance on Multiple Sclerosis: A Mendelian Randomization Study.. Current neuropharmacology. 2026; doi:10.2174/011570159X468669260626223524.
APA
Yalin Liu, Jiaoyan Yang, Jingyang Su, Liying Hao (2026). High Levels of Plasma Neurturin Partially Mediate the Protective Effect of Reduced Ruminococcus2 Abundance on Multiple Sclerosis: A Mendelian Randomization Study.. Current neuropharmacology. https://doi.org/10.2174/011570159X468669260626223524
GB/T 7714
Yalin Liu, Jiaoyan Yang, Jingyang Su, Liying Hao. High Levels of Plasma Neurturin Partially Mediate the Protective Effect of Reduced Ruminococcus2 Abundance on Multiple Sclerosis: A Mendelian Randomization Study.[J]. Current neuropharmacology, 2026 doi:10.2174/011570159X468669260626223524.
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