Association between gut microbiota and gastrointestinal cancer: a two-sample bi-directional Mendelian randomization study

Qing Su; Chen Jin; Zhiyuan Bo; Yi Yang; Jingxian Wang; Juejin Wang; Junxi Zhou; Yaqing Chen; Hao Zeng; Gang Chen; Yi Wang

doi:10.3389/fmicb.2023.1181328

Association between gut microbiota and gastrointestinal cancer: a two-sample bi-directional Mendelian randomization study

Front Microbiol. 2023 Jul 18:14:1181328. doi: 10.3389/fmicb.2023.1181328. eCollection 2023.

Authors

Qing Su¹, Chen Jin², Zhiyuan Bo³, Yi Yang¹, Jingxian Wang¹, Juejin Wang¹, Junxi Zhou¹, Yaqing Chen¹, Hao Zeng¹, Gang Chen³, Yi Wang¹

Affiliations

¹ Department of Epidemiology and Biostatistics, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China.
² Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
³ Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Abstract

Background: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Mendelian randomization; causal relationship; gastrointestinal cancer; gut microbiota; instrumental variable.