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

Frontiers in Microbiology

Microbiology

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

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

关键词: gut microbiota;    gastrointestinal cancer;    Mendelian randomization;    instrumental variable;    causal relationship;   

DOI  :  10.3389/fmicb.2023.1181328

 received in 2023-03-07, accepted in 2023-07-04,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundThe 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 methodsSummary-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.ResultsWe 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.ConclusionOur 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.

【 授权许可】

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Copyright © 2023 Su, Jin, Bo, Yang, Wang, Wang, Zhou, Chen, Zeng, Chen and Wang.