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Updated: Jul 20, 2025
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Association between gut microbiota and gastrointestinal cancer: a two-sample bi-directional Mendelian randomization
Qing Su1, Chen Jin2, Zhiyuan Bo3
1Department of Epidemiology and Biostatistics, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China.
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.
