肠道微生物群、血浆代谢物、炎症细胞因子与腹主动脉瘤之间的因果关系:孟德尔随机研究。

IF 1.5 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Clinical and Experimental Hypertension Pub Date : 2024-12-31 Epub Date: 2024-08-12 DOI:10.1080/10641963.2024.2390419
Chaozhong Li, Zhengqing Liu, Siqian Yang, Wanrong Li, Bo Liang, Haoyu Chen, Yujia Ye, Fang Wang, Xiaoqing Liu, Yongliang Jiang, Haiying Wu, Yunzhu Peng, Zhaohui Meng
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引用次数: 0

摘要

背景:肠道微生物群、循环代谢物、炎性细胞因子和腹主动脉瘤(AAA)的发病机制之间显然存在复杂的相互联系,其因果动态尚未得到全面阐明。本研究的主要目的是阐明肠道微生物群介导的血浆代谢物、炎性细胞因子与 AAA 的潜在因果关系:我们利用了主要由欧洲血统个体组成的全基因组关联研究的数据,包括四个主要肠道微生物群特征、233个血浆代谢物特征(N = 136,016)、91个炎症细胞因子特征(N = 14,824)和AAA特征(N = 1,458,875)。孟德尔随机化(Mendelian randomization,MR)以双样本的形式被用作研究肠道微生物群与 AAA 发病之间潜在因果关系的工具。此外,我们还采用了两步MR法来分析血浆代谢物和炎症细胞因子对肠道微生物群与AAA之间关系的影响,并确定介导的部分:结果:我们的研究结果表明,5个菌门或同科细菌、175种血浆代谢物和7种炎症因子与AAA存在因果关系。其中,从不同的 GWAS 数据中发现的同门或同科的 5 种细菌与 AAA 密切相关。其中,两种表现为负因果关系,三种表现为正因果关系。我们发现,真菌门和震旦梭菌科(Oscillospiraceae)可能会降低罹患 AAA 的风险,而普氏菌科(Prevotellaceae)、沙氏菌科(Sutterellaceae)和氨基杆菌科(Aminobacteriaceae)可能会增加罹患 AAA 的风险。进一步筛选表明,真菌门id.1672(GCST90017114)可能通过降低中/小高密度脂蛋白(HDL)中的甘油三酯水平而对AAA具有保护作用:磁共振分析确定了从肠道微生物群到血浆循环代谢物和炎性细胞因子再到 AAA 发病机制的因果关系。肠道菌群和某些生物标志物的作用可为 AAA 的诊断提供参考,并有助于 AAA 疾病的预防、诊断和治疗。
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Causal relationship between gut microbiota, plasma metabolites, inflammatory cytokines and abdominal aortic aneurysm: a Mendelian randomization study.

Background: Complex interconnections are evident among gut microbiota, circulating metabolites, inflammatory cytokines, and the pathogenesis of abdominal aortic aneurysms (AAA), with the causal dynamics yet to be comprehensively elucidated. The primary objective of this study was to elucidate the potential causal relationships involving gut microbiota-mediated plasma metabolites, inflammatory cytokines, and AAA.

Methods: We utilized data from genome-wide association studies predominantly comprising individuals of European ancestry, encompassing four major gut microbiota signatures, 233 plasma metabolite signatures (N = 136,016), 91 inflammatory cytokine signatures (N = 14,824), and AAA signatures (N = 1,458,875). Mendelian randomization (MR), employed in a two-sample format, was utilized as a tool to investigate the potential causal pathways from gut microbiota to the development of AAA. Additionally, a two-step MR approach was employed to dissect the impact of plasma metabolites and inflammatory cytokines on the relationship between gut microbiota and AAA and to ascertain the mediated fractions.

Results: Our findings indicate that five phylum or family-identical bacteria, 175 plasma metabolites, and seven inflammatory factors are causally associated with AAA. Among them, five bacterial species from the same phylum or family, identified from different GWAS data, were strongly associated with AAA. Of these, two exhibited negative causality and three exhibited positive causality. We found that the phylum Firmicutes and the families Oscillospiraceae might reduce the risk of AAA, whereas the families Prevotellaceae, Sutterellaceae, and Aminobacteriaceae might increase the risk of AAA. Further screening indicated that phylum Firmicutes id.1672 (GCST90017114) may confer a protective effect against AAA by reducing triglyceride levels in medium/small high-density lipoprotein (HDL).

Conclusion: MR analysis has delineated a causal pathway from gut microbiota, through plasma circulating metabolites and inflammatory cytokines, to the pathogenesis of AAA. The role of intestinal flora and certain biomarkers may provide a reference for the diagnosis of AAA, and contribute to the prevention, diagnosis, and treatment of AAA disease.

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来源期刊
CiteScore
3.90
自引率
0.80%
发文量
66
审稿时长
6-12 weeks
期刊介绍: Clinical and Experimental Hypertension is a reputable journal that has converted to a full Open Access format starting from Volume 45 in 2023. While previous volumes are still accessible through a Pay to Read model, the journal now provides free and open access to its content. It serves as an international platform for the exchange of up-to-date scientific and clinical information concerning both human and animal hypertension. The journal publishes a wide range of articles, including full research papers, solicited and unsolicited reviews, and commentaries. Through these publications, the journal aims to enhance current understanding and support the timely detection, management, control, and prevention of hypertension-related conditions. One notable aspect of Clinical and Experimental Hypertension is its coverage of special issues that focus on the proceedings of symposia dedicated to hypertension research. This feature allows researchers and clinicians to delve deeper into the latest advancements in this field. The journal is abstracted and indexed in several renowned databases, including Pharmacoeconomics and Outcomes News (Online), Reactions Weekly (Online), CABI, EBSCOhost, Elsevier BV, International Atomic Energy Agency, and the National Library of Medicine, among others. These affiliations ensure that the journal's content receives broad visibility and facilitates its discoverability by professionals and researchers in related disciplines.
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