Impact of gut microbiome, plasma metabolites, peripheral immune cells, and circulating inflammatory protein on chronic spontaneous urticaria: Bidirectional 2-sample Mendelian randomization study and mediation analysis.

Authors

Lijun Deng, Yuxu Yao, Qian Wang, Zhenzhong Lu, Enze Li, Ying Hu, Jialu Chen, Guoli Wang, Tingting Yu, Jiang Ji, Qingqing Jiao

Published in

The journal of allergy and clinical immunology. Global. Volume 5. Issue 3. Pages 100686. Epub Mar 24, 2026.

Abstract

Growing evidence links gut microbiota to chronic spontaneous urticaria (CSU), yet causality and underlying mediators remain unclear.
We investigated causal relationships and potential mediators-specifically plasma metabolites, immune cells, and inflammatory proteins-through which gut microbes influence CSU risk.
We applied 2-sample Mendelian randomization (MR) to genome-wide association study (GWAS) data on 430 gut microbial taxa, 1,400 plasma metabolites, 731 immune cell traits, and 91 inflammatory proteins. Analyses used inverse variance weighted, MR-Egger, weighted median, and weighted mode estimators, complemented by sensitivity, mediation, multivariable MR, and Bayesian colocalization tests for shared causal variants.
Eight gut taxa, 79 metabolites, 25 immune cell phenotypes, and 3 inflammatory proteins showed suggestive associated with CSU (all false discovery rate > .05). Galactonate mediated the effect of Paraprevotella on CSU, while N-acetyl leucine mediated the protective effect of Bacteroides; only the latter remained significant in multivariable MR. Immune cells and inflammatory proteins showed no significant mediation. Bayesian colocalization provided no evidence of shared causal variants between CSU and any of the 4 trait categories.
Gut microbiota may suggestively influence CSU risk via specific metabolite pathways, particularly N-acetyl leucine, though colocalization did not support shared genetic causality and no association survived multiple testing correction at false discovery rate < .05. These findings offer hypothesis-generating insights and candidate targets for further functional validation.

PMID:
42011428
Bibliographic data and abstract were imported from PubMed on 10 Sep 2026.

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