Mendelian Randomization Highlights Gut Microbiota of Short-chain Fatty Acids' Producer as Protective Factor of Cerebrovascular Disease.

Shihang Luo, Rui Mao, Yi Li
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Abstract

Background: Recent research advancements have indicated a potential association between gut microbiota and cerebrovascular diseases, although the precise causative pathways and the directionality of this association remain to be fully elucidated.

Objective: This study utilized a bidirectional two-sample Mendelian Randomization (MR) methodology to explore the causal impact of gut microbiota compositions on the risk of cerebrovascular disease.

Methods: Genome-wide Association Study (GWAS) data pertaining to gut microbiota were obtained from the MiBioGen consortium. For Ischemic Stroke (IS), Transient Ischemic Attack (TIA), Vascular Dementia (VD), and Subarachnoid Hemorrhage (SAH), GWAS summary data were sourced from the FinnGen consortium, the IEU Open GWAS project, and the GWAS catalog, respectively.

Results: Our MR analyses identified that specific bacterial strains, notably those involved in the production of Short-chain Fatty Acids (SCFAs), including Barnesiella, Ruminococcus torques group, and Coprobacter, serve as protective factors against IS, TIA, and SAH. Linkage Disequilibrium Score Regression (LDSC) analysis corroborated a significant genetic correlation between these gut microbiota strains and various forms of cerebrovascular disease. In contrast, reverse MR analysis failed to establish a bidirectional causal relationship between genetically inferred gut microbiota profiles and these cerebrovascular conditions.

Conclusion: This investigation has pinpointed particular strains of gut microbiota that play protective or detrimental roles in cerebrovascular disease pathogenesis. These findings offer valuable insights that could be pivotal for the clinical management, prevention, and treatment of cerebrovascular diseases.

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孟德尔随机化突显短链脂肪酸的肠道微生物群是脑血管疾病的保护因素。
背景:最近的研究进展表明,肠道微生物群与脑血管疾病之间存在潜在关联:最近的研究进展表明,肠道微生物群与脑血管疾病之间存在潜在关联,但这种关联的确切致病途径和方向性仍有待全面阐明:本研究采用双向双样本孟德尔随机化(MR)方法,探讨肠道微生物群组成对脑血管疾病风险的因果影响:全基因组关联研究(GWAS)中有关肠道微生物群的数据来自 MiBioGen 联盟。缺血性中风(IS)、短暂性脑缺血发作(TIA)、血管性痴呆(VD)和蛛网膜下腔出血(SAH)的全基因组关联研究(GWAS)摘要数据分别来自FinnGen联盟、IEU开放GWAS项目和GWAS目录:我们的磁共振分析发现,特定的细菌菌株,尤其是那些参与生产短链脂肪酸(SCFAs)的菌株,包括Barnesiella、Ruminococcus torques group和Coprobacter,是IS、TIA和SAH的保护因子。连锁变异平衡分数回归(LDSC)分析证实了这些肠道微生物群菌株与各种脑血管疾病之间存在显著的遗传相关性。与此相反,反向磁共振分析未能在基因推断的肠道微生物群特征与这些脑血管疾病之间建立双向因果关系:这项调查确定了在脑血管疾病发病机制中起保护或有害作用的特定肠道微生物菌株。这些发现为脑血管疾病的临床管理、预防和治疗提供了宝贵的见解。
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