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探讨肠道微生物群对胶质母细胞瘤的因果影响:一项双向孟德尔随机化研究。

Investigating the causal impact of gut microbiota on glioblastoma: a bidirectional Mendelian randomization study.

机构信息

The First Clinical Medical College of Gannan Medical University, Ganzhou City, 341000, Jiangxi Province, China.

Department of Neurosurgery, First Affiliated Hospital of Gannan Medical University, Qingnian Road, Ganzhou City, 341000, Jiangxi Province, China.

出版信息

BMC Genomics. 2023 Dec 18;24(1):784. doi: 10.1186/s12864-023-09885-2.

DOI:10.1186/s12864-023-09885-2
PMID:38110895
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10726622/
Abstract

BACKGROUND

Currently, the influence of microbiota on the occurrence, progression, and treatment of cancer is a topic of considerable research interest. Therefore, based on the theory of the gut-brain axis proved by previous studies, our objective was to uncover the causal relationship between glioblastoma and the gut microbiome using Mendelian randomization analysis.

METHODS

We conducted a bidirectional Mendelian randomization study using summary statistics of gut microbiota derived from the MiBioGen consortium, the largest database of gut microbiota. Summary statistics for glioblastoma were obtained from IEU OpenGWAS project, which included 91 cases and 218,701 controls. We assessed the presence of heterogeneity and horizontal pleiotropy in the analyzed data. We primarily employed the inverse variance weighting method to investigate the causal relationship between gut microbiota and glioblastoma after excluding cases of horizontal pleiotropy. Four other analysis methods were employed as supplementary. Excluding abnormal results based on leave-one-out sensitivity analysis. Finally, reverse Mendelian randomization analysis was performed.

RESULTS

Four genus-level taxa and one family-level taxa exhibited causal associations with glioblastoma. And these results of reverse Mendelian randomization analysis shown glioblastoma exhibited causal associations with three genus-level taxa and one family-level taxa. However, the Prevotella7(Forward, P=0.006, OR=0.34, 95%CI:0.158-0.732; Reverse, P=0.004, OR=0.972, 95%CI:0.953-0.991) shown the causal associations with glioblastoma in the bidirectional Mendelian randomization.

CONCLUSIONS

In this bidirectional Mendelian randomization study, we identified five gut microbiota species with causal associations to glioblastoma. However, additional randomized controlled trials are required to clarify the impact of gut microbiota on glioblastoma and to reveal its precise mechanisms.

摘要

背景

目前,微生物组对癌症发生、发展和治疗的影响是一个备受关注的研究课题。因此,基于先前研究证实的肠-脑轴理论,我们旨在通过孟德尔随机化分析揭示胶质母细胞瘤与肠道微生物组之间的因果关系。

方法

我们使用 MiBioGen 联盟(最大的肠道微生物组数据库)提供的肠道微生物组汇总统计数据进行了双向孟德尔随机化研究。胶质母细胞瘤的汇总统计数据来自 IEU OpenGWAS 项目,其中包括 91 例病例和 218701 例对照。我们评估了分析数据中存在的异质性和水平多效性。在排除水平多效性病例后,我们主要采用逆方差加权法来研究肠道微生物组与胶质母细胞瘤之间的因果关系。还采用了其他四种分析方法作为补充。基于单倍型缺失敏感性分析排除异常结果。最后进行了反向孟德尔随机化分析。

结果

有四个属水平分类群和一个科水平分类群与胶质母细胞瘤存在因果关联。而反向孟德尔随机化分析的结果显示,胶质母细胞瘤与三个属水平分类群和一个科水平分类群存在因果关联。然而,在双向孟德尔随机化中,普雷沃氏菌 7(正向,P=0.006,OR=0.34,95%CI:0.158-0.732;反向,P=0.004,OR=0.972,95%CI:0.953-0.991)与胶质母细胞瘤呈因果关联。

结论

在这项双向孟德尔随机化研究中,我们确定了五种与胶质母细胞瘤具有因果关联的肠道微生物组物种。然而,需要进一步的随机对照试验来阐明肠道微生物组对胶质母细胞瘤的影响,并揭示其确切机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a02/10726622/907bf3ca7fee/12864_2023_9885_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a02/10726622/a41d425ce8dc/12864_2023_9885_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a02/10726622/8e436d1354dd/12864_2023_9885_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a02/10726622/61e5ba0f6636/12864_2023_9885_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a02/10726622/fbf9bce2144b/12864_2023_9885_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a02/10726622/907bf3ca7fee/12864_2023_9885_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a02/10726622/a41d425ce8dc/12864_2023_9885_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a02/10726622/8e436d1354dd/12864_2023_9885_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a02/10726622/61e5ba0f6636/12864_2023_9885_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a02/10726622/fbf9bce2144b/12864_2023_9885_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a02/10726622/907bf3ca7fee/12864_2023_9885_Fig5_HTML.jpg

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