【摘要】 目的：肠道菌群和血液代谢物与荨麻疹的发展有关，但在东亚人群中的具体因果关系尚不完全清楚。本研究拟使用孟德尔随机化(Mendelian randomization,MR)分析来阐明东亚人群中肠道菌群、血液代谢物与荨麻疹之间的因果关系和中介效应。方法：从公开的全基因组关联研究(Genome-Wide Association Studies,GWAS)数据集中收集500种肠道菌群、112种血液代谢物和荨麻疹的汇总统计数据。使用双向MR分析探索肠道微生物群和血液代谢物与荨麻疹之间的因果关系。采用逆方差加权(inverse variance weighted,IVW)法作为主分析方法，MR-Egger、加权中位数法、简单模式法、加权模式法作为补充分析，异质性、水平多效性和留一分析进行敏感性分析。采用中介分析评估血液代谢物在肠道菌群和荨麻疹因果途径中的潜在中介作用。结果：MR分析结果显示：有12种肠道菌群与荨麻疹有因果关联，9种肠道菌群，如MF0017＿半乳糖降解(OR=1.461,95%CI 1.098～1.944,P=0.009)丰度的增加是荨麻疹的危险因素。3种肠道菌群，如MF0001＿阿拉伯木聚糖降解(OR=0.846,95%CI 0.737～0.973,P=0.019)丰度增加是荨麻疹的保护因素。此外，6种血液代谢物与荨麻疹有因果关联，其中，荨麻疹的发病风险随空腹血糖(fasting plasma glucose, FPG)的升高而升高(OR=1.971, 95%CI 1.089～3.567, P=0.025)。中介分析结果表明FPG介导MF0001＿阿拉伯木聚糖降解对荨麻疹的影响，解释了11.30%的影响。结论：本研究发现了东亚人群中与荨麻疹相关的特定肠道菌群和血液代谢物，其中阿拉伯木聚糖降解可能通过降低FPG来减轻荨麻疹的风险。这为通过调节肠道菌群和血糖管理干预荨麻疹的发生提供了遗传学依据。更多还原

【Abstract】 Objective: Gut microbiota(GM) and blood metabolites are associated with the development of urticaria, yet their specific causal relationships in East Asian populations remain unclear. This study aims to elucidate the causal and mediating relationships among GM, blood metabolites, and urticaria in East Asians using Mendelian randomization(MR) analysis.Methods: Summary-level statistics for 500 GM taxa, 112 blood metabolites, and urticaria were obtained from publicly available Genome-Wide Association Studies(GWAS) datasets. Bidirectional MR analyses were performed to examine causal associations among the GM, blood metabolites, and urticaria. The inverse variance weighted(IVW) method served as the primary analytical approach, supplemented by MR-Egger, weighted median, simple mode, and weighted mode methods. Sensitivity analyses included heterogeneity tests, horizontal pleiotropy assessments, and leave-one-out analyses. Mediation analysis was conducted to evaluate the potential mediating effects of blood metabolites on the causal pathways between GM and urticaria.Results: MR analyses identified 12 GM taxa exhibiting significant causal effects on urticaria susceptibility. Nine taxa, such as MF0017＿galactose＿degradation(OR=1.461, 95% CI 1.098 to 1.944, P=0.009), were associated with increased urticaria risk. Three taxa, such as MF0001＿arabinoxylan＿degradation(OR=0.846, 95% CI 0.737 to 0.973, P=0.019), showed protective effects with increased abundance. Additionally, 6 blood metabolites demonstrated causal associations with urticaria. Notably, the risk of developing urticaria increases with rising fasting plasma glucose(FPG) levels(OR=1.971, 95% CI 1.089 to 3.567, P=0.025). Mediation analysis further demonstrated that FPG partially mediated the protective effect of MF0001＿arabinoxylan＿degradation on urticaria, accounting for 11.30% of the total effect.Conclusion: This study has delineated specific GM taxa and blood metabolites that hold causal relevance to urticaria in East Asian populations. Notably, arabinogalactan degradation potentially mitigates urticaria risk via reducing FPG concentrations, offering genetic evidence to support therapeutic strategies targeting GM modulation and glucose regulation.更多还原