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口腔微生物群与癫痫风险之间的因果关系:来自东亚人群孟德尔随机化分析的证据。

Causal relationship between oral microbiota and epilepsy risk: Evidence from Mendelian randomization analysis in East Asians.

作者信息

Zhao Chenyang, Chen Fei, Li Qiong, Zhang Wei, Peng Lixiu, Yue Chaoyan

机构信息

The First People's Hospital of Chenzhou, Chenzhou, China.

The First Affiliated Hospital of Jinan University, Guangzhou, China.

出版信息

Epilepsia Open. 2024 Dec;9(6):2419-2428. doi: 10.1002/epi4.13074. Epub 2024 Oct 9.

DOI:10.1002/epi4.13074
PMID:39382490
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11633697/
Abstract

OBJECTIVE

Gut microbiota can traverse into the brain, activate the vagus nerve, and modulate immune responses and inflammatory processes, thereby influencing the onset of epileptic seizures. However, research on oral microbiota and epilepsy remains limited, and observational studies have been inconsistent. We aim to estimate the potential links between oral microbiota and epilepsy and elucidate which specific oral microbes may directly influence the pathogenesis of epilepsy.

METHODS

A two-sample MR analysis was conducted using genome-wide association study (GWAS) data specific to OM and epilepsy in East Asian individuals. Single nucleotide polymorphisms (SNPs) independent of confounders served as instrumental variables (IVs) to deduce causality. MR methodologies, including inverse variance weighted (IVW), MR-Egger, weighted median, and weighed mode methods, were utilized. Sensitivity analysis, including Cochrane's Q test, MR-Egger intercept test, and leave-one-out analysis, was applied to confirm the robustness of results.

RESULTS

Among the 3117 bacterial taxa examined, we observed that 14 OM, like s_Streptococcus_mitis, s_Streptococcus_pneumoniae, and s_Haemophilus, were positively associated with epilepsy, while 7 OM, like g_Fusobacterium and g_Aggregatibacter, were negatively related to epilepsy. The MR-Egger intercept suggested that no evidence of horizontal pleiotropy was observed (p > 0.05). The leave-one-out analysis validated the robustness of the results.

SIGNIFICANCE

This study underscores the effect of OM on epilepsy, suggesting potential mechanisms between the OM and epilepsy. Further investigation into the potential role of the OM is needed to enhance our in-depth understanding of the pathogenesis of epilepsy.

PLAIN LANGUAGE SUMMARY

Previous research has demonstrated that the microbiota may influence the onset of epileptic seizures. We applied 3117 oral microbiota from the newest publicly available database of East Asian populations. Mendelian randomization analysis was utilized to estimate the causal relationship between oral microbiota and epilepsy. Our results showed that a causal effect exists between 21 oral microbiota and epilepsy. We provided genetic evidence for risk assessment and early intervention in epilepsy.

摘要

目的

肠道微生物群可进入大脑,激活迷走神经,并调节免疫反应和炎症过程,从而影响癫痫发作的发生。然而,关于口腔微生物群与癫痫的研究仍然有限,且观察性研究结果并不一致。我们旨在评估口腔微生物群与癫痫之间的潜在联系,并阐明哪些特定的口腔微生物可能直接影响癫痫的发病机制。

方法

利用东亚人群中特定于口腔微生物群(OM)和癫痫的全基因组关联研究(GWAS)数据进行两样本孟德尔随机化分析。独立于混杂因素的单核苷酸多态性(SNP)用作工具变量(IV)来推断因果关系。采用了多种孟德尔随机化方法,包括逆方差加权法(IVW)、MR-Egger法、加权中位数法和加权模式法。应用敏感性分析,包括Cochrane's Q检验、MR-Egger截距检验和留一法分析,以确认结果的稳健性。

结果

在检测的3117个细菌分类群中,我们观察到14种口腔微生物群,如缓症链球菌、肺炎链球菌和嗜血杆菌属,与癫痫呈正相关,而7种口腔微生物群,如具核梭杆菌属和聚集杆菌属,与癫痫呈负相关。MR-Egger截距表明未观察到水平多效性的证据(p>0.05)。留一法分析验证了结果的稳健性。

意义

本研究强调了口腔微生物群对癫痫的影响,提示了口腔微生物群与癫痫之间的潜在机制。需要进一步研究口腔微生物群的潜在作用,以加深我们对癫痫发病机制的深入理解。

通俗易懂的总结

先前的研究表明微生物群可能影响癫痫发作的发生。我们应用了东亚人群最新公开可用数据库中的3117种口腔微生物群。利用孟德尔随机化分析来评估口腔微生物群与癫痫之间的因果关系。我们的结果表明21种口腔微生物群与癫痫之间存在因果效应。我们为癫痫的风险评估和早期干预提供了遗传证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd4c/11633697/2a7906e3a53d/EPI4-9-2419-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd4c/11633697/fba4d89de97a/EPI4-9-2419-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd4c/11633697/9e153762cc57/EPI4-9-2419-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd4c/11633697/2a7906e3a53d/EPI4-9-2419-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd4c/11633697/fba4d89de97a/EPI4-9-2419-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd4c/11633697/9e153762cc57/EPI4-9-2419-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd4c/11633697/2a7906e3a53d/EPI4-9-2419-g003.jpg

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