Gao Bingjun, Wang Zhe, Wang Kunyao, Lei Yinghan, Zhuang Yan, Zhou Zhonghua, Chen Junfei
Department of Pediatric Surgery, Qilu Hospital of Shandong University, Jinan, China.
Front Microbiol. 2024 Mar 28;15:1363776. doi: 10.3389/fmicb.2024.1363776. eCollection 2024.
The objective of this study is to investigate the causal relationship between gut microbiota and juvenile idiopathic arthritis, and to identify and quantify the potential role of plasma metabolites as mediators.
Using summary-level data from genome-wide association studies, a two-sample Mendelian randomization was conducted involving 131 gut microbiota genus, 1,400 plasma metabolites, and juvenile idiopathic arthritis. Additionally, a two-step approach was employed to quantify the proportion of the effect of gut microbiota on juvenile idiopathic arthritis mediated by plasma metabolites. Effect estimation primarily utilized Inverse Variance Weighting, with further validation using Bayesian weighted Mendelian randomization.
In our MR analysis, a positive correlation was observed between and the risk of juvenile idiopathic arthritis, while showed a negative correlation with juvenile idiopathic arthritis risk. Mediation analysis indicated that Furaneol sulfate levels acted as a mediator between and juvenile idiopathic arthritis, with an indirect effect proportion of 19.94, 95% CI [8.86-31.03%].
Our study confirms a causal relationship between specific microbial genus and juvenile idiopathic arthritis, and computes the proportion of the effect mediated by plasma metabolites, offering novel insights for clinical interventions in juvenile idiopathic arthritis.
本研究旨在探讨肠道微生物群与幼年特发性关节炎之间的因果关系，并确定和量化血浆代谢物作为中介的潜在作用。
利用全基因组关联研究的汇总水平数据，进行了一项两样本孟德尔随机化研究，涉及131个肠道微生物群属、1400种血浆代谢物和幼年特发性关节炎。此外，采用两步法来量化肠道微生物群对血浆代谢物介导的幼年特发性关节炎影响的比例。效应估计主要采用逆方差加权法，并使用贝叶斯加权孟德尔随机化进行进一步验证。
在我们的孟德尔随机化分析中，观察到[此处原文缺失具体微生物群属或代谢物名称]与幼年特发性关节炎风险呈正相关，而[此处原文缺失具体微生物群属或代谢物名称]与幼年特发性关节炎风险呈负相关。中介分析表明，硫酸呋喃酮水平在[此处原文缺失具体微生物群属或代谢物名称]与幼年特发性关节炎之间起中介作用，间接效应比例为19.94，95%可信区间[8.86 - 31.03%]。
我们的研究证实了特定微生物属与幼年特发性关节炎之间的因果关系，并计算了血浆代谢物介导的效应比例，为幼年特发性关节炎的临床干预提供了新的见解。
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