肠道菌群与胃肠癌密切相关，但肠道菌群与胃肠癌的因果关系尚未完全确定。我们进行了这项双样本曼德尔-拉宾曼因果推断（MR）研究，以揭示肠道菌群对胃肠癌的潜在因果效应。肠道菌群的摘要级遗传数据来自MiBioGen联盟和荷兰肠道菌群计划。六种胃肠癌的摘要统计数据来自英国生物库。我们使用逆方差加权（IVW）法、MR-鲁棒调整配置分数（MR-RAPS）法和加权中位数（WM）法评估肠道菌群与胃肠癌之间的潜在因果联系。此外，我们进行了敏感性分析和逆向MR分析。我们发现了21个细菌分类和胃肠癌之间的潜在因果关联（在所有三种MR方法中p值< 0.05）。其中，在Bonferroni修正后，门径微生物门（OR: 0.17, 95% CI: 0.05-0.59, p = 0.005）与肝内胆管细胞癌之间保持强烈的负相关，而芽孢杆菌目（OR: 1.67, 95% CI: 1.23-2.26, p = 0.001）与胰腺癌之间保持强烈的正相关。逆向MR分析显示，胃肠癌与17种微生物分类在所有三种MR方法中均相关。其中，经Bonferroni修正后发现结肠癌与梭菌科1家族保持强烈的负相关（OR: 0.91, 95% CI: 0.86-0.96, p = 0.001）。我们的研究揭示了特定微生物分类对胃肠癌的潜在因果效应，可能为通过特定肠道细菌预防和治疗胃肠癌提供了新的见解。© 2023 Su, Jin, Bo, Yang, Wang, Wang, Zhou, Chen, Zeng, Chen and Wang.

The gut microbiome is closely related to gastrointestinal (GI) cancer, but the causality of gut microbiome with GI cancer has yet to be fully established. We conducted this two-sample Mendelian randomization (MR) study to reveal the potential causal effect of gut microbiota on GI cancer.Summary-level genetic data of gut microbiome were derived from the MiBioGen consortium and the Dutch Microbiome Project. Summary statistics of six GI cancers were drawn from United Kingdom Biobank. Inverse-variance-weighted (IVW), MR-robust adjusted profile score (MR-RAPS), and weighted-median (WM) methods were used to evaluate the potential causal link between gut microbiota and GI cancer. In addition, we performed sensitivity analyses and reverse MR analyses.We identified potential causal associations between 21 bacterial taxa and GI cancers (values of p < 0.05 in all three MR methods). Among them, phylum Verrucomicrobia (OR: 0.17, 95% CI: 0.05-0.59, p = 0.005) retained a strong negative association with intrahepatic cholangiocarcinoma after the Bonferroni correction, whereas order Bacillales (OR: 1.67, 95% CI: 1.23-2.26, p = 0.001) retained a strong positive association with pancreatic cancer. Reverse MR analyses indicated that GI cancer was associated with 17 microbial taxa in all three MR methods, among them, a strong inverse association between colorectal cancer and family Clostridiaceae1 (OR: 0.91, 95% CI: 0.86-0.96, p = 0.001) was identified by Bonferroni correction.Our study implicates the potential causal effects of specific microbial taxa on GI cancer, potentially providing new insights into the prevention and treatment of GI cancer through specific gut bacteria.Copyright © 2023 Su, Jin, Bo, Yang, Wang, Wang, Zhou, Chen, Zeng, Chen and Wang.