■复杂的相互联系在肠道微生物群中很明显,循环代谢物,炎性细胞因子,和腹主动脉瘤(AAA)的发病机制,因果动力学还有待全面阐明。这项研究的主要目的是阐明涉及肠道微生物群介导的血浆代谢物的潜在因果关系。炎性细胞因子,和AAA。
■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,包括四个主要的肠道微生物群特征,233血浆代谢物特征(N=136,016),91炎性细胞因子特征(N=14,824),和AAA签名(N=1,458,875)。孟德尔随机化(MR),采用双样本格式,被用作研究从肠道微生物群到AAA发展的潜在因果途径的工具。此外,我们采用两步MR方法来分析血浆代谢物和炎性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.
■我们的发现表明五个门或家族相同的细菌,175种血浆代谢物,7种炎症因子与AAA有因果关系。其中,来自同一门或家族的五种细菌,从不同的GWAS数据中识别出,与AAA密切相关。其中,两人表现出负因果关系,三人表现出正因果关系。我们发现Firmicutes门和Oscillospiraceae科可以降低AAA的风险,而普雷沃科,菊科,和氨基杆菌科可能增加AAA的风险。进一步的筛选表明,Firmicutes门id.1672(GCST90017114)可以通过降低中/小型高密度脂蛋白(HDL)中的甘油三酸酯水平而对AAA产生保护作用。
■MR分析描绘了肠道微生物群的因果途径,通过血浆循环代谢物和炎症细胞因子,AAA的发病机制。肠道菌群和某些生物标志物的作用可能为AAA的诊断提供参考,并有助于预防,诊断,和治疗AAA疾病。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.