关键词: Mendelian randomisation analysis bidirectional causality gut microbiota juvenile idiopathic arthritis uveitis

Mesh : Humans Mendelian Randomization Analysis Gastrointestinal Microbiome / genetics Arthritis, Juvenile / microbiology genetics Genome-Wide Association Study Uveitis / microbiology etiology genetics Genetic Predisposition to Disease Polymorphism, Single Nucleotide

来  源:   DOI:10.3389/fimmu.2024.1356414   PDF(Pubmed)

Abstract:
UNASSIGNED: The gut microbiota significantly influences the onset and progression of juvenile idiopathic arthritis (JIA) and associated uveitis (JIAU); however, the causality remains unclear. This study aims to establish a causal link between gut microbiota and JIA or JIAU.
UNASSIGNED: Using publicly available genome-wide association studies (GAWS) summary data, we conducted a two-sample Mendelian randomisation (MR) analysis employing various methods, namely inverse variance weighted (IVW), simple mode, weighted mode, weighted median and MR-Egger regression methods, to assess the causal association between JIA or JIAU and gut microbiota. Sensitivity analyses, including Cochrane\'s Q test, MR-Egger intercept test, leave-one-out analysis and MR-PRESSO, were performed to evaluate the robustness of the MR results. Subsequently, reverse MR analysis was conducted to determine causality between gene-predicted gut microbiota abundance and JIA or JIAU.
UNASSIGNED: The MR analysis revealed a causal association between gut microbiota abundance variations and JIA or JIAU risk. Specifically, the increased abundance of genus Ruminococcaceae UCG013 (OR: 0.055, 95%CI: 0.006-0.103, p = 0.026) and genus Ruminococcaceae UCG003 (β: 0.06, 95%CI: 0.003-0.117, p = 0.041) correlated with an increased risk of JIA, while genus Lachnospiraceae UCG001 (OR: 0.833, 95%CI: 0.699~0.993, p = 0.042) was associated with a reduced risk of JIA, among others. Sensitivity analysis confirmed MR analysis robustness.
UNASSIGNED: This study provides substantial evidence supporting a causal association between genetically predicted gut microbiota and JIA or JIAU. It highlights the significant role of intestinal flora in JIA or JIAU development, suggesting their potential as novel biomarkers for diagnosis and prevention. These findings offer valuable insights to mitigate the impact of JIA or JIAU.
摘要:
肠道菌群显著影响幼年特发性关节炎(JIA)和相关葡萄膜炎(JIAU)的发病和进展;然而,因果关系尚不清楚。这项研究旨在建立肠道微生物群与JIA或JIAU之间的因果关系。
使用公开的全基因组关联研究(GAWS)汇总数据,我们采用各种方法进行了双样本孟德尔随机化(MR)分析,即逆方差加权(IVW),简单模式,加权模式,加权中位数和MR-Egger回归方法,评估JIA或JIAU与肠道微生物群之间的因果关系。敏感性分析,包括Cochrane的Q测试,MR-Egger截距测试,漏报分析和MR-PRESSO,进行评估MR结果的稳健性。随后,进行反向MR分析以确定基因预测的肠道微生物群丰度与JIA或JIAU之间的因果关系.
MR分析揭示了肠道微生物群丰度变化与JIA或JIAU风险之间的因果关系。具体来说,RuminococcaceaeUCG013(OR:0.055,95CI:0.006-0.103,p=0.026)和RuminococaceaeUCG003(β:0.06,95CI:0.003-0.117,p=0.041)的丰度增加与JIA的风险增加相关,而LachnospileaceaeUCG001(OR:0.833,95CI:0.699〜0.993,p=0.042)与JIA风险降低有关,在其他人中。灵敏度分析证实了MR分析的鲁棒性。
这项研究提供了大量证据,支持遗传预测的肠道微生物群与JIA或JIAU之间的因果关系。它强调了肠道菌群在JIA或JIAU发育中的重要作用,提示它们作为诊断和预防的新型生物标志物的潜力。这些发现为减轻JIA或JIAU的影响提供了有价值的见解。
公众号