Guo Wenqian, Hong Er, Ma Han, Wang Ji, Wang Qi
College of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
National Institute of Traditional Chinese Medicine Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China.
Front Immunol. 2025 Mar 21;16:1436888. doi: 10.3389/fimmu.2025.1436888. eCollection 2025.
Asthma is a chronic inflammatory disorder arising from incompletely understood heterogenic gene-environment interactions. This study aims to investigate causal relationships among gut microbiota, skin microbiota, plasma metabolomics, white blood cells subtype, immune cells, inflammatory proteins, inflammatory cytokines, and asthma.
First, two-sample Mendelian randomization analysis was used to identify causal relationships. The summary statistics of 412 gut microbiota traits (N = 7 738), 150 skin microbiota traits (N = 579), 1 400 plasma metabolite traits (N = 8 299), white blood cells subtype counts (N = 746 667), 731 immune cell traits (N = 3 669), 91 circulating inflammatory proteins (N = 14 744), 41 inflammatory cytokine traits (N = 8 293), and asthma traits (N = 244 562) were obtained from publicly available genome-wide association studies. Inverse-variance weighted regression was used as the primary Mendelian randomization method. A series of sensitivity analyses was performed to test the robustness of causal estimates. Subsequently, mediation analysis was performed to identify the pathway from gut or skin microbiota to asthma mediated by plasma metabolites, immune cells, and inflammatory proteins.
Mendelian randomization revealed the causal effects of 31 gut bacterial features (abundances of 19 bacterial pathways and 12 microbiota), 10 skin bacterial features, 108 plasma metabolites (81 metabolites and 27 ratios), 81 immune cells, five circulating inflammatory proteins, and three inflammatory cytokines and asthma. Moreover, the mediation analysis results supported the mediating effects of one plasma metabolite, five immunophenotypes, and one inflammatory protein on the gut or skin microbiota in asthma pathogenesis.
The findings of this study support a causal relationship among gut microbiota, skin microbiota, plasma metabolites, immune cells, inflammatory proteins, inflammatory cytokines, and asthma. Mediating pathways through which the above factors may affect asthma were proposed. The biomarkers and mediation pathways identified in this work provide new insights into the mechanism of asthma and contribute to its prevention and treatment.
哮喘是一种慢性炎症性疾病，其源于尚未完全明确的异质性基因-环境相互作用。本研究旨在探究肠道微生物群、皮肤微生物群、血浆代谢组学、白细胞亚型、免疫细胞、炎症蛋白、炎症细胞因子与哮喘之间的因果关系。
首先，采用两样本孟德尔随机化分析来确定因果关系。从公开的全基因组关联研究中获取了412个肠道微生物群特征（N = 7738）、150个皮肤微生物群特征（N = 579）、1400个血浆代谢物特征（N = 8299）、白细胞亚型计数（N = 746667）、731个免疫细胞特征（N = 3669）、91种循环炎症蛋白（N = 14744）、41种炎症细胞因子特征（N = 8293）以及哮喘特征（N = 244562）的汇总统计数据。采用逆方差加权回归作为主要的孟德尔随机化方法。进行了一系列敏感性分析以检验因果估计的稳健性。随后，进行中介分析以确定肠道或皮肤微生物群通过血浆代谢物、免疫细胞和炎症蛋白介导导致哮喘的途径。
孟德尔随机化揭示了31个肠道细菌特征（19条细菌途径和12种微生物群的丰度）、10个皮肤细菌特征、108种血浆代谢物（81种代谢物和27种比率）、81种免疫细胞、5种循环炎症蛋白、3种炎症细胞因子与哮喘之间的因果效应。此外，中介分析结果支持了一种血浆代谢物、5种免疫表型和一种炎症蛋白在哮喘发病机制中对肠道或皮肤微生物群的中介作用。
本研究结果支持肠道微生物群、皮肤微生物群、血浆代谢物、免疫细胞、炎症蛋白、炎症细胞因子与哮喘之间存在因果关系。提出了上述因素可能影响哮喘的中介途径。本研究确定的生物标志物和中介途径为哮喘的发病机制提供了新的见解，并有助于其预防和治疗。
