背景:肠道菌群(GM)已被证明与许多胃肠道疾病有关,但其与胃食管反流病(GERD)和Barrett食管(BE)的因果关系尚未探讨。我们旨在通过孟德尔随机化(MR)分析揭示GM和GERD/BE与潜在介质之间的因果关系。
方法:从MiBioGenConsortium(N=18,340)和荷兰微生物组项目(N=7,738)中提取了GM(包括301个细菌分类群和205个代谢途径)的摘要统计,GERD和BE来自多性状荟萃分析(NGERD=602,604,NBE=56,429)。采用双向双样本MR分析和连锁不平衡评分回归(LDSC)探讨GM与GERD/BE的遗传相关性。对GERD/BE的危险因素进行中介MR分析,包括体重指数(BMI),体重,2型糖尿病,抑郁症(MDD),开始吸烟,酒精消费,和饮食摄入(包括碳水化合物,糖,脂肪,蛋白质摄入量),检测GM和GERD/BE之间的潜在介质。
结果:发现了11种细菌分类群和13种代谢途径与GERD相关,18个分类单元和5条途径与BE存在因果关系。中介MR分析表明,体重和BMI在这些关系中起着至关重要的作用。LDSC确定了1个分类单元和4个与GERD相关的代谢途径,和1个与BE相关的分类单元。prausnitzii物种对GERD(OR=1.087,95CI=1.01-1.17)和BE(OR=1.388,95CI=1.03-1.86)均具有暗示性影响,LDSC确定了它们的相关性。反向MR表明BE影响10个分类单元和4个途径。
结论:这项研究建立了肠道菌群与GERD/BE之间的因果关系。并确定了可能的调解员。它为肠道微生物群在宿主GERD和BE的发展和进展中的作用提供了新的见解。
BACKGROUND: Gut microbiota(GM) have been proven associated with lots of gastrointestinal diseases, but its causal relationship with Gastroesophageal reflux disease(GERD) and Barrett\'s esophagus(BE) hasn\'t been explored. We aimed to uncover the causal relation between GM and GERD/BE and potential mediators by utilizing Mendelian Randomization(MR) analysis.
METHODS: Summary statistics of GM(comprising 301 bacteria taxa and 205 metabolism pathways) were extracted from MiBioGen Consortium(N = 18,340) and Dutch Microbiome Project(N = 7,738), GERD and BE from a multitrait meta-analysis(NGERD=602,604, NBE=56,429). Bidirectional two-sample MR analysis and linkage disequilibrium score regression(LDSC) were used to explore the genetic correlation between GM and GERD/BE. Mediation MR analysis was performed for the risk factors of GERD/BE, including Body mass index(BMI), weight, type 2 diabetes, major depressive disorder(MDD), smoking initiation, alcohol consumption, and dietary intake(including carbohydrate, sugar, fat, protein intake), to detect the potential mediators between GM and GERD/BE.
RESULTS: 11 bacterial taxa and 13 metabolism pathways were found associated with GERD, and 18 taxa and 5 pathways exhibited causal relationship with BE. Mediation MR analysis suggested weight and BMI played a crucial role in these relationships. LDSC identified 1 taxon and 4 metabolism pathways related to GERD, and 1 taxon related to BE. Specie Faecalibacterium prausnitzii had a suggestive impact on both GERD(OR = 1.087, 95%CI = 1.01-1.17) and BE(OR = 1.388, 95%CI = 1.03-1.86) and LDSC had determined their correlation. Reverse MR indicated that BE impacted 10 taxa and 4 pathways.
CONCLUSIONS: This study established a causal link between gut microbiota and GERD/BE, and identified the probable mediators. It offers new insights into the role of gut microbiota in the development and progression of GERD and BE in the host.