肠道菌群和代谢相关脂肪性肝病的因果关联:一项双样本孟德尔随机化研究

Causal associations between gut microbiome and metabolic associated fatty liver disease: A two-sample mendelian randomization study

目的肠道菌群在代谢相关脂肪性肝病(metabolic associated fatty liver disease,MAFLD)的发展过程中扮演着重要角色,但两者之间的具体联系尚不清楚,本研究旨在从遗传学的角度推断两者因果关系。方法从MiBioGen联盟发表的肠道微生物组GWAS(genome-wide association studies)研究中获取汇总统计数据,筛选遗传变异点作为工具变量(instrumental variables,IV)。利用反向方差加权(inverse variance weighted,IVW),加权中位数(weighted median,WE)和MR-Egger回归进行双样本孟德尔随机化分析。通过敏感性分析检验异质性、水平多效性和结果的稳定性。结果IVW结果显示,乳酸杆菌科(OR=0.830,95%CI 0.708~0.973,P<0.05),克里斯滕森菌属R7群(OR=0.737,95%CI 0.589~0.920,P<0.01),罗氏菌属(OR=0.501,95%CI 0.732-0.989,P<0.05)可能是MAFLD发生的保护因素,而放线菌科(OR=1.250,95%CI 1.020~1.532,P<0.05),草酸杆菌科(OR=1.101,95%CI1.007~1.205,P<0.05),放线菌目(OR=1.250,95%CI 1.020~1.533,P<0.05),NB1n目(OR=1.110,95%CI 1.006~1.226,P<0.05),瘤胃球菌科UCG-005群(OR=1.181,95%CI 1.013~1.377,P<0.05)可能是MAFLD发生的危险因素。结论本研究探究了肠道菌群与MAFLD的因果关系,筛选出与MAFLD相关的肠道菌群,这些菌群可能成为新的生物标志物,为MAFLD的预防和治疗提供新的治疗思路,促进对肠-肝轴的认识和理解。

Objective Gut microbiota plays an important role in the occurrence of metabolic associated fatty liver disease(MAFLD),but the specific relationship between the two is still unclear.The present study aimed to address this issue from a genetic perspective.Methods Statistical data were obtained from gut microbiome Genome-Wide Association Studies(GWAS)published by the MiBioGen consortium,and genetic variation points were screened as instrumental variables(IV).Two-sample Mendelian randomization analysis was performed by inverse variance weighted(IVW),weighted median(WE)and MR-Egger regression.In addition,sensitivity analyses were performed to test for heterogeneity,horizontal pleiotropy,and stability of the results.Results IVW results showed that:family.Lactobacillaceae(OR=0.830,95%CI 0.708~0.973,P<0.05),genus.Christensenellaceae R.7group(OR=0.737,95%CI 0.589~0.920,P<0.01),genus.Roseburia(OR=0.501,95%CI 0.732~0.989,P<0.05)were protective factors against MAFLD, while family. Actinomycetaceae (OR=1. 250, 95%CI 1. 020~1. 532, P<0. 05), family. Oxalobacteraceae (OR=1. 101, 95%CI 1. 007~1. 205, P<0. 05), order. Actinomycetales (OR=1. 250, 95%CI 1. 020~1. 533, P<0. 05), order. NB1n (OR=1. 110, 95%CI 1. 006~1. 226, P<0. 05), genus. Ruminococcaceae UCG005 (OR=1. 181, 95%CI 1. 013~1. 377, P<0. 05) might be a risk factor for MAFLD. Conclusion We study revealed the causal relationship between gut microbiota and MAFLD, and screened out gut microbiota related to MAFLD. The microbiota may become new biomarkers, provide new therapeutic ideas for the prevention and treatment of MAFLD, and the study further promote our understanding and understanding of the gut liver axis.