基于"肺合皮毛"理论探讨皮肤菌群和肺动脉高压之间的因果关系及潜在通路预测OA
Exploring the causality and potential pathway prediction between skin microbiota and pulmonary arterial hypertension based on the theory of"lung associating with skin"
目的:基于中医"肺合皮毛"理论,采用孟德尔随机化(Mendelian randomization,MR)方法探讨皮肤菌群与肺动脉高压的因果关联,预测调控皮肤菌群从而干预肺动脉高压的潜在通路,为临床预防和治疗策略提供新思路.方法:从 NHGRI-EBI GWAS 数据库和 FinnGen 数据库获取皮肤菌群与肺动脉高压的全基因组关联研究(geneme-wide association study,GWAS)数据,使用 R 语言进行 MR 分析,以逆方差加权法(inverse variance weighting,IVW)为主要方法评估因果关系,并通过异质性检验、水平多效性检验及留一法敏感性分析验证结果的稳健性.利用FUMA 平台识别工具变量邻近基因,通过DAVID 数据库对邻近基因进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析,探索肺动脉高压发病的潜在通路.结果:MR 分析结果显示,前臂背侧的金黄杆菌属、肘窝的棒状杆菌属及伯克霍尔德氏菌目与肺动脉高压发病风险呈负相关;前额皮脂的厚壁菌门与肺动脉高压发病风险呈正相关.总共筛选出50 个核心基因,GO 和 KEGG 富集分析结果提示,其可能主要通过补体和凝血级联通路、过氧化物酶体通路等参与肺动脉高压发病.结论:本研究通过 MR 分析揭示了特定皮肤菌群与肺动脉高压发病风险存在因果关系,预测出其潜在作用机制,主要涉及补体和凝血级联通路、过氧化物酶体通路.这为从"肺合皮毛"理论视角深入探究肺动脉高压的发病机制提供了依据.
Objective:Based on the theory of"lung associating with skin"in traditional Chinese medicine(TCM),this study aims to explore the causality between skin microbiota and pulmonary hypertension(PH)using the Mendelian randomization(MR)method,predict the potential pathways through which regulating the skin microbiota may intervene in PH,and provide new insights for clinical prevention and treatment strategies.Methods:Genome-wide association study(GWAS)data on skin microbiota and PH were obtained from the NHGRI-EBI GWAS Catalog and FinnGen database.MR analysis was performed using R software,with the inverse variance weighting(IVW)method as the primary approach to evaluate causalities.The robustness of the results was verified through heterogeneity tests,horizontal pleiotropy tests,and leave-one-out sensitivity analyses.The FUMA platform was used to identify genes adjacent to instrumental variables,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of these adjacent genes were conducted via the DAVID database to explore potential pathways involved in the pathogenesis of PH.Results:MR analysis showed that Chryseobacterium(from the dorsal forearm),Corynebacterium(from the elbow fossa),and Burkholderiales(from the elbow fossa)were negatively associated with the risk of PH.Firmicutes(from the forehead sebum)was positively associated with the risk of PH.A total of 50 core genes were screened out.The GO and KEGG enrichment analyses suggested that these genes may be involved in the pathogenesis of PH mainly through the complement and coagulation cascades pathway and the peroxisome pathway.Conclusion:This study reveals,through MR analysis,that specific skin microbiota have a causality with the risk of PH,and predicts that their potential mechanisms of action involve the complement and coagulation cascades pathway and the peroxisome pathway.This provides a scientific basis for in-depth exploration of the pathogenesis of PH from the perspective of the"lung associating with skin"theory.
胡中梅;郑天琪;方曾江楠;王时光
安徽中医药大学第一临床医学院,安徽 合肥,230031安徽中医药大学第一临床医学院,安徽 合肥,230031安徽中医药大学第一临床医学院,安徽 合肥,230031安徽中医药大学第一附属医院,安徽 合肥,230031
医药卫生
肺动脉高压皮肤菌群肺合皮毛孟德尔随机化通路预测
Pulmonary hypertensionSkin microbiotaLung associating with skinMendelian randomizationPathway prediction
《中医临床研究》 2026 (1)
28-34,7
安徽省教育厅高校中青年人才培养项目(JNFX2024026)全国老中医药专家学术经验继承工作项目(国中医药人教函[2022]76号)安徽中医药传承创新科研项目(2024ZYYXH148)安徽中医药大学探索性科研项目(AHUCM2024TS106).
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