東アジア人における腸内細菌叢、血液代謝物、および蕁麻疹との因果関係：メンデルランダム化研究

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.

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.

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.

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.