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探讨肠道微生物组与主动脉瘤疾病之间的关联:双向两样本孟德尔随机分析。

Investigating the association between gut microbiome and aortic aneurysm diseases: a bidirectional two-sample Mendelian randomization analysis.

机构信息

Department of Cardiovascular Surgery, Tianjin Medical University General Hospital, Tianjin, China.

Pediatric Cardiac Surgery, Fuwai Central China Cardiovascular Hospital, Zhengzhou, China.

出版信息

Front Cell Infect Microbiol. 2024 Jul 30;14:1406845. doi: 10.3389/fcimb.2024.1406845. eCollection 2024.

Abstract

OBJECTIVE

This study aims to investigate the associations between specific bacterial taxa of the gut microbiome and the development of aortic aneurysm diseases, utilizing Mendelian Randomization (MR) to explore these associations and overcome the confounding factors commonly present in observational studies.

METHODS

Employing the largest available gut microbiome and aortic aneurysm Genome-Wide Association Study databases, including MiBioGen, Dutch Microbiome Project, FinnGen, UK Biobank, and Michigan Genomics Initiative, this study performs two-sample bidirectional MR analyses. Instrumental variables, linked to microbiome taxa at significant levels, were selected for identifying relationships with abdominal aortic aneurysms (AAA), thoracic aortic aneurysms (TAA), and aortic dissection (AD). Methods like inverse variance weighted, MR-PRESSO, MR-Egger, weighted median, simple mode, and mode-based estimate were used for MR analysis. Heterogeneity was assessed with the Cochran Q test. MR-Egger regression and MR-PRESSO addressed potential unbalanced horizontal pleiotropy.

RESULTS

The analysis did not find any evidence of statistically significant associations between the gut microbiome and aortic aneurysm diseases after adjusting for the false discovery rate (FDR). Specifically, while initial results suggested correlations between 19 taxa and AAA, 25 taxa and TAA, and 13 taxa with AD, these suggested associations did not hold statistical significance post-FDR correction. Therefore, the role of individual gut microbial taxa as independent factors in the development and progression of aortic aneurysm diseases remains inconclusive. This finding underscores the necessity for larger sample sizes and more comprehensive studies to further investigate these potential links.

CONCLUSION

The study emphasizes the complex relationship between the gut microbiome and aortic aneurysm diseases. Although no statistically significant associations were found after FDR correction, the findings provide valuable insights and highlight the importance of considering gut microbiota in aortic aneurysm diseases research. Understanding these interactions may eventually contribute to identifying new therapeutic and preventive strategies for aortic aneurysm diseases.

摘要

目的

本研究旨在利用孟德尔随机化(MR)方法研究肠道微生物组中特定细菌分类群与主动脉瘤疾病发展之间的关联,以探讨这些关联并克服观察性研究中常见的混杂因素。

方法

本研究利用最大的肠道微生物组和主动脉瘤全基因组关联研究数据库,包括 MiBioGen、荷兰微生物组计划、FinnGen、英国生物银行和密歇根基因组倡议,进行了两样本双向 MR 分析。选择与微生物组分类群在显著水平上相关的工具变量,以确定与腹主动脉瘤(AAA)、胸主动脉瘤(TAA)和主动脉夹层(AD)的关系。采用逆方差加权、MR-PRESSO、MR-Egger、加权中位数、简单模式和基于模式的估计等方法进行 MR 分析。采用 Cochran Q 检验评估异质性。MR-Egger 回归和 MR-PRESSO 解决了潜在的不平衡水平偏倚问题。

结果

在调整了假发现率(FDR)后,该分析未发现肠道微生物组与主动脉瘤疾病之间存在统计学显著关联的证据。具体而言,尽管最初的结果表明 19 个分类群与 AAA 相关,25 个分类群与 TAA 相关,13 个分类群与 AD 相关,但这些关联在 FDR 校正后并不具有统计学意义。因此,个体肠道微生物分类群作为主动脉瘤疾病发展和进展的独立因素的作用仍不确定。这一发现强调了肠道微生物组与主动脉瘤疾病之间复杂的关系。尽管在 FDR 校正后没有发现统计学上显著的关联,但这些发现提供了有价值的见解,并强调了在主动脉瘤疾病研究中考虑肠道微生物群的重要性。了解这些相互作用可能最终有助于确定主动脉瘤疾病的新治疗和预防策略。

结论

本研究强调了肠道微生物组与主动脉瘤疾病之间的复杂关系。尽管在 FDR 校正后没有发现统计学上显著的关联,但这些发现提供了有价值的见解,并强调了在主动脉瘤疾病研究中考虑肠道微生物群的重要性。了解这些相互作用可能最终有助于确定主动脉瘤疾病的新治疗和预防策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7df5/11319299/e1ddad5fa009/fcimb-14-1406845-g001.jpg

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