肠道微生物群与胃肠道疾病的因果关系：一项孟德尔随机化研究。
Causal relationship between gut microbiota and gastrointestinal diseases: a mendelian randomization study.
机构信息
Department of Gastroenterology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, China.
Department of Rheumatology and Immunology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, International Science and Technology Cooperation base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China.
出版信息
J Transl Med. 2024 Jan 23;22(1):92. doi: 10.1186/s12967-024-04894-5.
BACKGROUND
Recent research increasingly highlights a strong correlation between gut microbiota and the risk of gastrointestinal diseases. However, whether this relationship is causal or merely coincidental remains uncertain. To address this, a Mendelian randomization (MR) analysis was undertaken to explore the connections between gut microbiota and prevalent gastrointestinal diseases.
METHODS
Genome-wide association study (GWAS) summary statistics for gut microbiota, encompassing a diverse range of 211 taxa (131 genera, 35 families, 20 orders, 16 classes, and 9 phyla), were sourced from the comprehensive MiBioGen study. Genetic associations with 22 gastrointestinal diseases were gathered from the UK Biobank, FinnGen study, and various extensive GWAS studies. MR analysis was meticulously conducted to assess the causal relationship between genetically predicted gut microbiota and these gastrointestinal diseases. To validate the reliability of our findings, sensitivity analyses and tests for heterogeneity were systematically performed.
RESULTS
The MR analysis yielded significant evidence for 251 causal relationships between genetically predicted gut microbiota and the risk of gastrointestinal diseases. This included 98 associations with upper gastrointestinal diseases, 81 with lower gastrointestinal diseases, 54 with hepatobiliary diseases, and 18 with pancreatic diseases. Notably, these associations were particularly evident in taxa belonging to the genera Ruminococcus and Eubacterium. Further sensitivity analyses reinforced the robustness of these results.
CONCLUSIONS
The findings of this study indicate a potential genetic predisposition linking gut microbiota to gastrointestinal diseases. These insights pave the way for designing future clinical trials focusing on microbiome-related interventions, including the use of microbiome-dependent metabolites, to potentially treat or manage gastrointestinal diseases and their associated risk factors.
背景
最近的研究越来越多地强调肠道微生物群与胃肠道疾病风险之间的强烈相关性。然而，这种关系是因果关系还是仅仅是巧合仍然不确定。为了解决这个问题，进行了一项孟德尔随机化（MR）分析，以探讨肠道微生物群与常见胃肠道疾病之间的联系。
方法
从全面的 MiBioGen 研究中获取了涵盖 211 个分类群（131 个属、35 个科、20 个目、16 个纲、9 个门）的肠道微生物群的全基因组关联研究（GWAS）汇总统计数据。从英国生物库、芬兰基因研究和各种广泛的 GWAS 研究中收集了与 22 种胃肠道疾病相关的遗传关联。MR 分析仔细评估了遗传预测的肠道微生物群与这些胃肠道疾病之间的因果关系。为了验证我们发现的可靠性，系统地进行了敏感性分析和异质性检验。
结果
MR 分析得出了 251 种遗传预测的肠道微生物群与胃肠道疾病风险之间存在因果关系的显著证据。这包括 98 种与上胃肠道疾病相关的关联，81 种与下胃肠道疾病相关的关联，54 种与肝胆疾病相关的关联，18 种与胰腺疾病相关的关联。值得注意的是，这些关联在属于 Ruminococcus 和 Eubacterium 属的分类群中尤为明显。进一步的敏感性分析增强了这些结果的稳健性。
结论
这项研究的结果表明，肠道微生物群与胃肠道疾病之间存在潜在的遗传易感性。这些发现为设计未来的临床试验铺平了道路，这些临床试验侧重于与微生物组相关的干预措施，包括使用微生物组依赖性代谢物，以潜在地治疗或管理胃肠道疾病及其相关的危险因素。
Zotero 插件