肠道微生物群与十二指肠疾病相互作用的遗传学见解：一项孟德尔随机化和贝叶斯加权研究。
Genetic insights into the gut microbiota-duodenal diseases interplay: A Mendelian randomization and Bayesian weighting study.
作者信息
Chen Xuehui, Chang Hong, Gao Chuanmei, Zhu Xiao
机构信息
The Second Affiliated Hospital, School of Ocean and Tropical Medicine, Guangdong Medical University, Zhanjiang, China.
Department of Pathology, Qingdao Third People's Hospital, Qingdao, China.
出版信息
Microb Pathog. 2025 Feb;199:107181. doi: 10.1016/j.micpath.2024.107181. Epub 2024 Nov 28.
BACKGROUND
Many observational studies have shown a close association between gut microbiota and the risk of various duodenal diseases. Therefore, we urgently explore the potential causal relationship between gut microbiota and some duodenal diseases, mainly including duodenal ulcers and duodenitis.
METHODS
We conducted Mendelian randomization (MR) studies using genetic instrumental variables for gut microbiota from GWAS and duodenal disease datasets. Causal relationships were examined using multiple MR methods with Bonferroni correction. Bayesian Weighted Mendelian Randomization (BWMR) assessed causal relationships, employing ELBO and weighted data. Reverse MR analysis was conducted on microbiota showing significant causal relationships with duodenal diseases.
RESULTS
Through MR analysis, we identified three gut microbiota that promote the occurrence of duodenal ulcers (family. Coriobacteriaceae: OR = 1.003; 95 % CI = 1.0005-1.0056; p = 0.016, genus.RuminococcaceaeUCG003: OR = 1.006; 95 % CI = 1.002-1.007; p = 0.002, order. Coriobacteriales: OR = 1.003; 95 % CI = 1.0005-1.0056; p = 0.016), one microbiota that inhibits the occurrence of duodenitis (family. Acidaminococcaceae: OR = 0.994; 95 % CI = 0.988-0.999; p = 0.046), and one microbiota that promotes the occurrence of duodenitis (genus.Eubacteriumcoprostanoligenesgroup: OR = 1.006; 95 % CI = 1.0005-1.013; p = 0.033). Further confirmation of the occurrence of duodenal ulcers and the production of family.Coriobacteriaceae and order.Coriobacteriales microbiota was obtained through reverse MR analysis, indicating that the occurrence of duodenal ulcers also promotes the growth of these microbiota.
CONCLUSION
Our study employs Mendelian randomization techniques to demonstrate a causal relationship between specific gut microbiota and duodenal ulcers and duodenitis. Additionally, our analysis suggests that duodenal ulcer occurrence promotes the growth of certain microbiota, emphasizing the intricate interplay between gut microbiota composition and these diseases.
背景
许多观察性研究表明肠道微生物群与各种十二指肠疾病的风险密切相关。因此，我们迫切需要探索肠道微生物群与某些十二指肠疾病之间的潜在因果关系，主要包括十二指肠溃疡和十二指肠炎。
方法
我们使用来自全基因组关联研究（GWAS）和十二指肠疾病数据集的肠道微生物群的遗传工具变量进行孟德尔随机化（MR）研究。使用多种MR方法并进行Bonferroni校正来检验因果关系。贝叶斯加权孟德尔随机化（BWMR）采用变分推断（ELBO）和加权数据来评估因果关系。对与十二指肠疾病显示出显著因果关系的微生物群进行反向MR分析。
结果
通过MR分析，我们确定了三种促进十二指肠溃疡发生的肠道微生物群（科氏杆菌科：比值比（OR）=1.003；95%置信区间（CI）=1.0005-1.0056；p=0.016，瘤胃球菌科UCG003属：OR=1.006；95%CI=1.002-1.007；p=0.002，科氏杆菌目：OR=1.003；95%CI=1.0005-1.0056；p=0.016），一种抑制十二指肠炎发生的微生物群（氨基酸球菌科：OR=0.994；95%CI=0.988-0.999；p=0.046），以及一种促进十二指肠炎发生的微生物群（真杆菌粪甾醇生成菌群：OR=1.006；95%CI=1.0005-1.013；p=0.033）。通过反向MR分析进一步证实了十二指肠溃疡的发生以及科氏杆菌科和科氏杆菌目的微生物群的产生，这表明十二指肠溃疡的发生也促进了这些微生物群的生长。
结论
我们的研究采用孟德尔随机化技术证明了特定肠道微生物群与十二指肠溃疡和十二指肠炎之间的因果关系。此外，我们的分析表明十二指肠溃疡的发生促进了某些微生物群的生长，强调了肠道微生物群组成与这些疾病之间复杂的相互作用。
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