Volume 23 Issue 6
Jun.  2025
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ZHANG Qiao, ZHOU Xuezhi, ZHANG Dechong, LIANG Shuqi, WU Xinjun, ZHU Shaohui. Bidirectional two-sample Mendelian randomization study on the causal association between gut microbiota and colorectal cancer[J]. Chinese Journal of General Practice, 2025, 23(6): 933-936. doi: 10.16766/j.cnki.issn.1674-4152.004036
Citation: ZHANG Qiao, ZHOU Xuezhi, ZHANG Dechong, LIANG Shuqi, WU Xinjun, ZHU Shaohui. Bidirectional two-sample Mendelian randomization study on the causal association between gut microbiota and colorectal cancer[J]. Chinese Journal of General Practice, 2025, 23(6): 933-936. doi: 10.16766/j.cnki.issn.1674-4152.004036

Bidirectional two-sample Mendelian randomization study on the causal association between gut microbiota and colorectal cancer

doi: 10.16766/j.cnki.issn.1674-4152.004036
Funds:

 LHGJ20210536

  • Received Date: 2025-01-27
    Available Online: 2025-09-04
  •   Objective  The complex pathogenesis of colorectal cancer (CRC) may be potentially linked to gut microbiota (GM); however, existing observational studies are limited by confounding factors in establishing a clear causal relationship. To explore the causal association between GM and CRC using a bidirectional two-sample Mendelian randomization (MR) method.  Methods  GWAS data on 471 GM species and CRC were collected, and strong instrumental variables (IVs) were selected. The causal effect was evaluated using the inverse variance weighted method (IVW), weighted median method (WME), MR-Egger method, simple mode method, and weighted mode method, with IVW as the primary approach. Bayesian weighted Mendelian randomization (BWMR) was further used for analysis, and the results were presented with ORs and 95% CIs. The reliability and robustness of the results were assessed through Cochran's Q test, MR-Egger intercept test, MR-PRESSO test, and leave-one-out sensitivity analysis. Finally, a reverse MR analysis was performed for GM species positively associated with CRC.  Results  IVW analysis showed that the genus Succinivibrionaceae (OR=0.819, 95% CI: 0.718-0.934, P=0.003), Alistipes shahii (OR=0.731, 95% CI: 0.573-0.933, P=0.012), Psychroserpens (OR=0.643, 95% CI: 0.492-0.840, P=0.001), and Prevotella buccae (OR=0.849, 95% CI: 0.737-0.977, P=0.022) were significantly associated with CRC. BWMR results were consistent with the IVW method, and no significant heterogeneity or horizontal pleiotropy was observed. Reverse MR analysis revealed no significant causal relationship between CRC and these four GM species (P>0.05).  Conclusion  The abundance of Succinivibrionaceae, Alistipes shahii, Psychroserpens, and Prevotella buccae is negatively correlated with the risk of CRC, suggesting that these GM species may be protective factors for CRC. Further research is needed to explore the mechanisms through which GM influences CRC development.

     

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