Wang Wencai, Liu Menghao, Wang Zun, Ma Luyao, Zhao Yongqiang, Ye Wei, Li Xianfeng
The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, People's Republic of China.
Juntendo University, Tokyo, Japan.
BMC Neurol. 2025 Jun 9;25(1):249. doi: 10.1186/s12883-025-04187-4.
Implying connections with gut microbiome and serum metabolites, idiopathic normal pressure hydrocephalus (INPH) emerges as a prevalent neuropsychiatric condition in the elderly. Our objective was to systematically evaluate the potential causality between gut microbiome, derived metabolites, and INPH through the implementation of Mendelian randomization (MR) methodology.
We utilized summary data from extensive genome-wide association studies, encompassing 196 gut microbiomes from the MiBioGen consortium (n = 18,340), 486 serum metabolites from the KORA and TwinsUK studies (n = 7,824), and individuals with INPH (case = 767, control = 375,610), for MR causal estimates. The leading analysis utilized the inverse-variance weighted (IVW) method, supplemented by weighted mode, MR-Egger, weighted median and simple mode approaches. Sensitivity analyses included MR-Egger intercept, Cochran's Q test, leave-one-out analysis and MR-PRESSO.
Our study primarily relied on the IVW method, confirming a causality between 9 genetically predicted abundance of gut microbiomes and INPH. We found an adverse correlation with genetically predicted abundance of order Clostridiales, genus Eubacteriumeligensgroup, genus Gordonibacter, genus Ruminococcus1 concerning INPH. Conversely, class Melainabacteria, genus Eubacteriumruminantiumgroup, genus Adlercreutzia, genus Dialister, genus RikenellaceaeRC9gutgroup potentially correlated with increased INPH risk. As for derived metabolites, IVW estimates indicated a causal connection between 25 genetically predicted serum metabolites and INPH. Sensitivity analysis underscored the robustness of our findings.
Our MR analysis provides evidence supporting the causality of certain gut microbial taxa and their derived metabolites on INPH. This underscores the potential for interventions targeting specific gut microbiota and derived metabolites in the treatment and prevention of INPH.
特发性正常压力脑积水（INPH）被认为与肠道微生物群和血清代谢物有关，是老年人中一种常见的神经精神疾病。我们的目标是通过实施孟德尔随机化（MR）方法，系统评估肠道微生物群、衍生代谢物与INPH之间的潜在因果关系。
我们利用了来自广泛全基因组关联研究的汇总数据，包括MiBioGen联盟的196种肠道微生物群（n = 18340）、KORA和TwinsUK研究的486种血清代谢物（n = 7824）以及INPH患者（病例 = 767，对照 = 375610），进行MR因果估计。主要分析采用逆方差加权（IVW）方法，并辅以加权模式、MR-Egger、加权中位数和简单模式方法。敏感性分析包括MR-Egger截距、 Cochr an's Q检验、留一法分析和MR-PRESSO。
我们的研究主要依赖IVW方法，证实了9种基因预测的肠道微生物群丰度与INPH之间存在因果关系。我们发现，关于INPH，基因预测的梭菌目、优杆菌属、戈登菌属、瘤胃球菌属1的丰度呈负相关。相反，黑素杆菌纲、反刍优杆菌属、阿德勒克雷茨菌属、戴利斯特菌属、理研菌科RC9肠道菌群可能与INPH风险增加相关。至于衍生代谢物，IVW估计表明25种基因预测的血清代谢物与INPH之间存在因果联系。敏感性分析强调了我们研究结果的稳健性。
我们的MR分析提供了证据，支持某些肠道微生物分类群及其衍生代谢物对INPH的因果关系。这突出了针对特定肠道微生物群和衍生代谢物进行干预在INPH治疗和预防中的潜力。
