通讯作者: 张涛, 9087958@qq.com

DOI：10.12201/bmr.202412.00049

Association Between Gut Microbiota and Liver Cirrhosis in East Asian Populations: A Mendelian Randomization Study

• 摘要：摘要：目的：利用孟德尔随机化（Mendelian randomization，MR）方法探究东亚人群肠道菌群与肝硬化之间的关联。方法：从国家基因库生命大数据平台中获取肠道菌群的全基因组关联分析研究（Genome wide association study,GWAS）数据集，IEU Open GWAS数据库中获取肝硬化的GWAS数据集，以肠道菌群为暴露因素，肝硬化为结局变量，采用逆方差加权法（inverse variance weighted，IVW）作为主分析方法、基于约束最大似然和模型平均法（constrained maximum likelihood and model averaging，cML-MA）为次要分析方法、验证肠道菌群与肝硬化之间的因果关系，并通过敏感性分析、留一法分析验证结果的稳健性。结果：以IVW为主分析方法初步发现16 种与肝硬化相关的肠道菌群，其中马文布兰特菌属、硫酸盐还原菌属、粪类杆菌属 、密螺旋体齿垢菌株、瘤胃菌科、血色胶菌属、福尼斯弧菌、梭菌属L2-50 、热厌氧菌属、光冈菌属的丰度升高，会增加患者肝硬化的风险；脱硫弧菌属、海尔氏梭菌、丙酸生产菌属、阿利斯特菌属、萨拉尼特氏类杆菌、迪克氏菌属的丰度升高，会降低患者肝硬化的风险；而cML-MA方法分析结果显示光冈菌属、梭菌属L2-50、马文布兰特菌属、粪类杆菌属、迪克氏菌属具有统计学意义，提示以上5种肠道菌群与肝硬化为强相关性。16种菌群异质性和水平多效性P＞0.05，无异质性和水平多效性，且“留一法”分析没有异常单个异常SNP。结论：本研究发现东亚人群中16种肠道菌群与肝硬化存在相关性，其中5种肠道菌群与肝硬化显著相关，为预防和治疗肝硬化提供了新的遗传学证据。

  关键词： 孟德尔随机化; 东亚人群; 肠道菌群; 肝硬化; 全基因组关联研究

   

  Abstract: Abstract: Objective: This study aims to explore the association between gut microbiota and liver cirrhosis in East Asian populations using Mendelian Randomization (MR) methods. Methods: To obtain the genome-wide association study (GWAS) datasets on gut microbiota from the National GeneBank Big Data Platform and the GWAS datasets on liver cirrhosis from the IEU Open GWAS database, using gut microbiota as the exposure factor and liver cirrhosis as the outcome variable. The main analytical method adopted is the inverse variance weighted (IVW) method, with the constrained maximum likelihood and model averaging (cML-MA) method as a secondary analysis method, to verify the causal relationship between gut microbiota and liver cirrhosis. The robustness of the results will be further validated through sensitivity analysis and leave-one-out analysis. Results: The primary IVW analysis preliminarily identified 16 gut microbiota species associated with liver cirrhosis. An increased abundance of Marvinbryantia, Desulfovibrio, Coprococcus, Treponema socranskii, Ruminococcaceae, Sanguinibacter, Vibrio furnissii, Clostridium L2-50, Thermanaerovibrio, and Mitsuokella was found to elevate the risk of liver cirrhosis. Conversely, an increased abundance of Desulfovibrio, Clostridium hathewayi, Propionibacterium, Allistipes, Bacteroides salanitiphilus, and Dyella was associated with a reduced risk of liver cirrhosis. The cML-MA analysis revealed statistical significance for Mitsuokella, Clostridium L2-50, Marvinbryantia, Coprococcus, and Dyella, indicating a strong correlation between these five gut microbiota species and liver cirrhosis. The heterogeneity and horizontal pleiotropy for 16 bacterial clusters showed P > 0.05, suggesting an absence of heterogeneity and horizontal pleiotropy, and the leave-one-out analysis did not identify any outlier SNPs. Conclusion: This research reveals an association between 16 gut microbiota and liver cirrhosis in the East Asian population, with 5 of these gut microbiota demonstrating a significant correlation with liver cirrhosis, offering new genetic insights for the prevention and treatment of liver cirrhosis.

  Key words: Mendelian randomization; East Asian population; gut microbiota; liver cirrhosis; genome-wide association study

  提交时间：2024-12-20

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  1	2024-10-30	bmr.202412.00049V1	下载

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