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

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

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1181328

DOI=10.3389/fmicb.2023.1181328

ISSN=1664-302X

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Materials and methods</title><p>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.</p></sec><sec><title>Results</title><p>We identified potential causal associations between 21 bacterial taxa and GI cancers (values of <italic>p</italic> &lt; 0.05 in all three MR methods). Among them, phylum <italic>Verrucomicrobia</italic> (OR: 0.17, 95% CI: 0.05–0.59, <italic>p</italic> = 0.005) retained a strong negative association with intrahepatic cholangiocarcinoma after the Bonferroni correction, whereas order <italic>Bacillales</italic> (OR: 1.67, 95% CI: 1.23–2.26, <italic>p</italic> = 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 <italic>Clostridiaceae1</italic> (OR: 0.91, 95% CI: 0.86–0.96, <italic>p</italic> = 0.001) was identified by Bonferroni correction.</p></sec><sec><title>Conclusion</title><p>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.</p></sec>