Yang Zhao, Yu Rong, Deng Wei, Wang Weihu
School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
Front Genet. 2022 Jun 9;13:894900. doi: 10.3389/fgene.2022.894900. eCollection 2022.
Lack of definitive evidence supports the putative hypothesis that gut microbiota dysbiosis is associated with Barrett's esophagus (BE). We conducted a two-sample Mendelian randomization study to assess the associations of 21 genera of human gut microbiota with BE. We identified independent genetic instruments for 21 genera of gut microbiota (including nine dominant genera, four core genera among individuals of European ancestry, and eight esophagus-specific genera of gut microbiota) from MiBioGen (up to 18,340 participants). We applied them to summary statistics from the largest publicly available genome-wide association study on BE (9,680 cases and 31,211 controls). We obtained the causal estimates of genetically predicted higher genera of gut microbiota and BE using the inverse variance weighting method. Sensitivity analyses included weighted median, MR-Egger, MR-RAPS, and MR-PRESSO. We found that genetically predicted higher (OR: 0.76 per unit increase in log odds of having BE, 95% CI: 0.70-0.83) and higher (OR: 0.75, 95% CI: 0.63-0.90) were significantly associated with a lower risk of BE. No associations of other genera of gut microbiota with BE were noted, apart from suggestive associations of higher (OR: 0.77; 95% CI: 0.61-0.99), higher (OR: 0.89; 95% CI: 0.80-0.99), and higher (OR: 0.76; 95% CI: 0.56-1.02) with a lower risk of BE, and higher (OR: 1.15; 95% CI: 0.99-1.33) with a higher risk of BE. This study suggests that higher and higher might protect against BE.
缺乏确凿证据支持肠道微生物群失调与巴雷特食管（BE）相关的假设。我们进行了一项两样本孟德尔随机化研究，以评估21种人类肠道微生物群属与BE的关联。我们从MiBioGen（多达18340名参与者）中确定了21种肠道微生物群属的独立遗传工具（包括9个优势属、欧洲血统个体中的4个核心属以及8个食管特异性肠道微生物群属）。我们将它们应用于关于BE的最大公开可用全基因组关联研究的汇总统计数据（9680例病例和31211名对照）。我们使用逆方差加权法获得了遗传预测的肠道微生物群属较高水平与BE的因果估计值。敏感性分析包括加权中位数、MR-Egger、MR-RAPS和MR-PRESSO。我们发现，遗传预测的较高水平（BE发生对数优势每增加一个单位，OR：0.76，95%CI：0.70-0.83）和较高水平（OR：0.75，95%CI：0.63-0.90）与BE风险较低显著相关。除了较高水平（OR：0.77；95%CI：0.61-0.99）、较高水平（OR：0.89；95%CI：0.80-0.99）和较高水平（OR：0.76；95%CI：0.56-1.02）与BE风险较低有提示性关联，以及较高水平（OR：1.15；95%CI：0.99-1.33）与BE风险较高有提示性关联外，未发现其他肠道微生物群属与BE有关联。这项研究表明，较高水平和较高水平可能预防BE。
