肠道菌群与糖尿病神经病变的因果关系:双样本孟德尔随机化分析

Causal relationship between intestinal flora and diabetic neuropathy:a two-sample Mendelian randomisation analysis

目的使用孟德尔随机化技术探索肠道菌群与糖尿病神经病变相关性。方法采用公共数据库Mi-BioGen研究的肠道菌群GWAS数据和芬兰数据库(The FinnGen)的糖尿病神经病变GWAS数据,根据预设的阈值提取与211种肠道菌群相对丰度显著相关的独立遗传位点作为工具变量,采用逆方差加权法进行分析,根据效应指标优势比和95%置信区间评估结果。此外,使用留一法、异质性检验及水平基因多效性检验验证结果的稳定性和可靠性。结果肠道菌群与糖尿病神经病变之间存在因果关系,其中产粪甾醇真杆菌属、放线菌门、双歧杆菌属、消化球菌科可能是糖尿病神经病变的保护性因素,而Christensenellaceae R7 group属、埃格特菌属、瘤胃球菌科UCG-013是糖尿病神经病变的潜在危险因素。结论产粪甾醇真杆菌属、放线菌门、双歧杆菌属、消化球菌科能减少糖尿病神经病变风险,而Christensenellaceae R7 group属、埃格特菌属、瘤胃球菌科UCG-013与糖尿病神经病变风险增加有关,我们的研究支持几个肠道菌群和糖尿病神经病变之间的潜在因果关系,需要进一步研究来探究肠道菌群如何影响糖尿病神经病变的发生发展。

Objective To explore the correlation between gut microbiota and diabetic neuropathy using Mendelian randomisation.Methods Using the GWAS data of gut microbiota from the public database MiBioGen study and the GWAS data of diabetic neuropathy from the Finnish database,independent genetic loci significantly associated with the relative abundance of 211 species of gut microbiota were extracted according to preset thresholds as instrumental variables.The analyses were mainly performed using the inverse variance weighting method,and the results were assessed based on the effect indicator Odds ratio and 95%confidence interval.In addition,the stability and reliability of the results were verified using the leave-one-out method,heterogeneity test,and horizontal gene pleiotropy test.Results The results showed a causal relationship between intestinal flora and diabetic neuropathy,in which genera Eubacterium coprostanoligenes,Actinobacteria,Bifidobacterium and Peptococcaceae might be protective factors against diabetic neuropathy,whereas Christensenellaceae R7 group,Eggerthella and Ruminococcaceae UCG-013 were potential risk factors for diabetic neuropathy.Conclusion Eubacterium coprostanoligenes,Actinobacteria,Bifidobacterium and Peptococcaceae reduced the risk of diabetic neuropathy,whereas the Christensenellaceae R7 group,Eggerthella and Ruminococcaceae UCG-013 were associated with an increased risk of diabetic neuropathy.Our study supports a potential causal relationship between several gut flora and diabetic neuropathy.Further studies are needed to investigate how gut flora affects the development of diabetic neuropathy.