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剖析肠道微生物群、血液代谢物与多形性胶质母细胞瘤之间的因果关系:一项两样本孟德尔随机化研究

Dissecting causal relationships between gut microbiota, blood metabolites, and glioblastoma multiforme: a two-sample Mendelian randomization study.

作者信息

Chen Xuan, Han Lihui, Xu Wenzhe

机构信息

Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, China.

Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, China.

出版信息

Front Microbiol. 2024 Jul 3;15:1403316. doi: 10.3389/fmicb.2024.1403316. eCollection 2024.

DOI:10.3389/fmicb.2024.1403316
PMID:39021629
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11251919/
Abstract

BACKGROUND

Given the increasing interest in the role of gut microbiota in glioblastoma multiforme (GBM), our objective was to examine the potential causal relationship between gut microbiota and GBM, as well as the mediating effects of specific metabolites.

METHODS

A bidirectional two-sample Mendelian randomization (MR) analysis was conducted to investigate the associations between 196 microbial taxa and GBM. A two-step MR technique was used to identify significant mediators in this relationship. Subsequently, a mediation analysis was performed to explore and quantify the mediating effects of specific metabolites on the causal relationship between gut microbiota and GBM.

RESULTS

Five taxa showed significant associations with GBM. Among them, [odds ratio (OR): 1.95; 95% confidence interval (CI): 1.21, 3.13;  = 0.005] and (OR: 1.81; 95% CI: 1.04, 3.15;  = 0.036) were positively correlated with the risk of GBM, while had a protective effect against GBM (OR: 0.45; 95% CI: 0.22, 0.89;  = 0.021). The mediation analysis revealed that the connections among and GBM were mediated by Methyl-4-hydroxybenzoate sulfate, phosphoethanolamine and dehydroepiandrosterone sulfate. Each of these accounted for 7.27, 7.98, and 8.65%, respectively.

CONCLUSION

Our study provides evidence supporting a potential causal association between certain gut microbiota taxa and GBM. The study highlights the central role of gut microbiota in GBM pathogenesis and their interactions with vital serum metabolites. This paves the way for potential novel therapeutic interventions in GBM management.

摘要

背景

鉴于肠道微生物群在多形性胶质母细胞瘤(GBM)中的作用日益受到关注,我们的目标是研究肠道微生物群与GBM之间的潜在因果关系,以及特定代谢物的中介作用。

方法

进行双向双样本孟德尔随机化(MR)分析,以研究196种微生物分类群与GBM之间的关联。采用两步MR技术来确定这种关系中的显著中介因素。随后,进行中介分析,以探索和量化特定代谢物对肠道微生物群与GBM之间因果关系的中介作用。

结果

5个分类群与GBM显示出显著关联。其中,[比值比(OR):1.95;95%置信区间(CI):1.21,3.13;P = 0.005]和(OR:1.81;95%CI:1.04,3.15;P = 0.036)与GBM风险呈正相关,而对GBM有保护作用(OR:0.45;95%CI:0.22,0.89;P = 0.021)。中介分析表明,和GBM之间的联系由硫酸甲基-4-羟基苯甲酸酯、磷酸乙醇胺和硫酸脱氢表雄酮介导。这些分别占7.27%、7.98%和8.65%。

结论

我们的研究提供了证据,支持某些肠道微生物分类群与GBM之间存在潜在因果关联。该研究突出了肠道微生物群在GBM发病机制中的核心作用及其与重要血清代谢物的相互作用。这为GBM管理中潜在的新型治疗干预措施铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d4a/11251919/91ea33e7e6c1/fmicb-15-1403316-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d4a/11251919/101e874d514a/fmicb-15-1403316-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d4a/11251919/c52c96a7ae11/fmicb-15-1403316-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d4a/11251919/91ea33e7e6c1/fmicb-15-1403316-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d4a/11251919/101e874d514a/fmicb-15-1403316-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d4a/11251919/c52c96a7ae11/fmicb-15-1403316-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d4a/11251919/91ea33e7e6c1/fmicb-15-1403316-g003.jpg

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