Graduate school, Dalian Medical University, Dalian, Dalian, China.
Department of Neurosurgery, Dalian Municipal Central Hospital, Dalian, China.
PLoS One. 2024 May 29;19(5):e0304403. doi: 10.1371/journal.pone.0304403. eCollection 2024.
In the realm of Gut-Brain axis research, existing evidence points to a complex bidirectional regulatory mechanism between gut microbiota and the brain. However, the question of whether a causal relationship exists between gut microbiota and specific types of brain tumors, such as gliomas, remains unresolved. To address this gap, we employed publicly available Genome-Wide Association Study (GWAS) and MIOBEN databases, conducting an in-depth analysis using Two-Sample Mendelian Randomization (MR).
We carried out two sets of MR analyses. The preliminary analysis included fewer instrumental variables due to a high genome-wide statistical significance threshold (5×10-8). To enable a more comprehensive and detailed analysis, we adjusted the significance threshold to 1×10-5. We performed linkage disequilibrium analysis (R2 <0.001, clumping distance = 10,000kb) and detailed screening of palindromic SNPs, followed by MR analysis and validation through sensitivity analysis.
Our findings reveal a causal relationship between gut microbiota and gliomas. Further confirmation via Inverse Variance Weighting (IVW) identified eight specific microbial communities related to gliomas. Notably, the Peptostreptococcaceae and Olsenella communities appear to have a protective effect, reducing glioma risk.
This study not only confirms the causal link between gut microbiota and gliomas but also suggests a new avenue for future glioma treatment.
在肠道-大脑轴的研究领域,现有的证据表明肠道微生物群和大脑之间存在复杂的双向调节机制。然而,肠道微生物群与特定类型的脑肿瘤(如神经胶质瘤)之间是否存在因果关系,这一问题仍未得到解决。为了解决这一差距,我们利用了公开的全基因组关联研究(GWAS)和 MIOBEN 数据库,通过两样本孟德尔随机化(MR)进行了深入分析。
我们进行了两组 MR 分析。初步分析由于全基因组统计显著性阈值较高(5×10-8),因此使用的工具变量较少。为了进行更全面和详细的分析,我们将显著性阈值调整为 1×10-5。我们进行了连锁不平衡分析(R2 <0.001,聚类距离=10,000kb)和回文 SNP 的详细筛选,然后进行了 MR 分析,并通过敏感性分析进行了验证。
我们的研究结果表明肠道微生物群与神经胶质瘤之间存在因果关系。通过逆方差加权(IVW)进一步确认,发现了与神经胶质瘤相关的八个特定微生物群落。值得注意的是,拟杆菌科和奥尔森菌科似乎具有保护作用,降低了神经胶质瘤的风险。
本研究不仅证实了肠道微生物群与神经胶质瘤之间的因果关系,还为未来的神经胶质瘤治疗提供了新的途径。