肠道微生物和肺功能(FEV1/FVC)的两样本孟德尔随机化研究及其在中医药领域应用的思考  

Two-sample Mendelian randomization study of gut microbiota and lung function(FEV1/FVC)and the thought on its application in the TCM field

作　　者：黄徐睿 马桢 李潇宁 张淇范 万鑫焱 郑浩旻 张瑜 王虹虹[1] Huang Xurui;Ma Zhen;Li Xiaoning;Zhang Qifan;Wan Xinyan;Zheng Haomin;Zhang Yu;Wang Honghong(Health Management Center,Third Clinical Medical College,Beijing University of Chinese Medicine,Beijing 100029,China;Beijing University of Chinese Medicine,Beijing 100029,China;Department of Pediatrics,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China;Department of Respiratory Medicine,Third Clinical Medical College,Beijing University of Chinese Medicine,Beijing 100029,China;Department of Special Geriatrics,Third Clinical Medical College,Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]北京中医药大学第三临床医学院健康管理中心,北京100029 [2]北京中医药大学,北京100029 [3]北京中医药大学东直门医院儿科,北京100700 [4]北京中医药大学第三临床医学院呼吸科,北京100029 [5]北京中医药大学第三临床医学院特需老年科,北京100029

出　　处：《国际中医中药杂志》2024年第6期698-706,共9页International Journal of Traditional Chinese Medicine

摘　　要：目的利用两样本孟德尔随机化(MR)法探讨肠道微生物与肺功能(FEV1/FVC)的因果关系及其在中医药领域的应用。方法MR法研究。采用公共数据库中MiBioGen联盟研究的肠道微生物全基因组关联研究(GWAS)数据和IEU OpenGWAS发布的肺功能(FEV1/FVC)的GWAS数据,根据预设的阈值提取工具变量。以逆方差加权法(IVW)分析为主,根据效应指标β值和95%CI评估结果,当IVW分析有统计学意义时进行敏感性分析,使用留一法、异质性检验、水平基因多效性检验、MR-Egger回归截距分析等方法验证结果的稳定性与可靠性。结果通过IVW共确定了10种肠道微生物和肺功能(FEV1/FVC)之间的因果关系,分别为拟杆菌科S24.7组(β=-0.029,P=0.015)、梭菌科BB60组(β=-0.028、P=0.040)、链球菌科(β=-0.056,P=0.042)、毛螺菌属FCS020组(β=0.025,P=0.029)、乳球菌属(β=-0.024,P=0.038)、消化球菌属(β=0.025,P=0.049)、瘤胃球菌属UCG011(β=-0.030,P=0.038)、瘤胃球菌属2(β=0.028,P=0.033)、土孢杆菌属(β=-0.030,P=0.018)、蓝菌门(β=0.027,P=0.039)。留一法分析显示结果稳定,且可剔除异质性和水平基因多效性对因果效应估计产生的影响。结论肠道微生物在肺功能变化中可能发挥一定作用,本研究在一定程度上印证了中医“肺与大肠相表里”理论思想,可为中医药研究方向提供一定参考。Objective To explore the causal relationship between gut microbiota and lung function(FEV1/FVC)using two-sample Mendelian randomization method;To explore its application in the TCM field.Methods This was a Mendelian randomization study.The GWAS data of gut microbiota from the MiBioGen consortium study and the GWAS data of lung function(FEV1/FVC)published by IEU OpenGWAS in the public database were used,and instrumental variables were extracted according to prespecified thresholds.The inverse variance weighted method(IVW)was mainly used for analysis.The results were evaluated according to the effect indicatorβvalue and 95%CI.When the IVW method was statistically significant,further sensitivity analysis was performed.Leave-one-out test,heterogeneity test,horizontal gene pleiotropy test and MR-Egger regression intercept analysis were used to verify the stability and reliability of the results.Results A total of 10 causal relationships between gut microbiota and lung function(FEV1/FVC)were determined using the IVW method:family.BacteroidalesS24.7group(β=-0.029,P=0.015),family.ClostridialesvadinBB60group(β=-0.028,P=0.040),family.Streptococcaceae(β=-0.056,P=0.042),genus.LachnospiraceaeFCS020group(β=0.025,P=0.029),genus.Lactococcus(β=-0.024,P=0.038),genus.Peptococcus(β=0.025,P=0.049),genus.RuminococcaceaeUCG011(β=-0.030,P=0.038),genus.Ruminococcus2(β=0.028,P=0.033),genus.Terrisporobacter(β=-0.030,P=0.018),phylum.Cyanobacteria(β=0.027,P=0.039).Leave-one-out analysis showed that the results were stable,and the effects of heterogeneity and horizontal gene pleiotropy on causal effect estimation could be removed.Conclusion The gut microbiota may play a role in the changes of lung function,which to a certain extent confirms the TCM theory of"exterior-interior relationship between the lung and large intestine",and can provide certain reference for the research direction of TCM.

关 键 词：孟德尔随机化分析 胃肠道微生物群 肺功能 因果关系 中医药 

分 类 号：R242[医药卫生—中医临床基础]