The Causal Link Between Colon Adenocarcinoma and Gut Microbiota: A Bi-Directional Mendelian Randomization Study

Wu ZY, Huang SK, Ye YY, Zheng WT, Chen HL, Hou XT, Shen RJ, Vithayaphalert V, Juengpanich S* and Zheng HM

Department of Surgical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, China Department of Immunology and Pathogen Biology, School of Basic Medical Sciences, Hangzhou Normal University, China Department of Clinical Medicine, The First Clinical School of Guangzhou Medical University, China School of Medicine, Zhejiang University, Hangzhou, China Department of Internal Medicine, King memorial Chulalongkorn Hospital, Thailand These authors contributed equally to this work

^*Correspondance to: He-Ming Zheng 

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Abstract:

Purpose: This study aims to explore the causal relationships between gut microbiota and colon cancer using a bidirectional Mendelian Randomization (MR) approach. Methods: We employed a bidirectional MR research, utilizing genetic variants as Instrumental Variables (IVs) to infer causality. Genetic data for gut microbiota were obtained from the MiBioGen Consortium, encompassing 211 gut microbiota taxa, while data for colon cancer were sourced from the FinnGen Consortium, including 290,221 participants. We conducted MR analyses to evaluate the influence of gut microbiota on colon cancer and vice versa. IVs were selected based on stringent criteria to ensure the robustness of our findings. Multiple statistical methods, including Inverse Variance Weighted (IVW) and MR-Egger regression, were used to assess causality. Results: Forward MR analysis identified eight gut microbiota taxa associated with colon cancer risk. Notably, Enterobacteriales (order), Peptococcaceae (family), and genera like Dialister and Roseburia were protective factors, whereas Enterobacteriaceae, Porphyromonadaceae, and Escherichia-Shigella were risk factors. Reverse MR analysis revealed that colon cancer was associated with changes in the abundance of eight gut microbiota taxa, including an increase in Lactobacillales (order) and Streptococcaceae (family), with genera such as Eubacterium_eligens_group and Roseburia being protective. Conclusion: Our bidirectional MR study underscores a significant causal relationship between gut microbiota and colon cancer. Specific gut microbiota taxa were identified as either risk or protective factors for colon cancer, suggesting potential avenues for microbiota-targeted interventions in colon cancer prevention and treatment. Further research is warranted to elucidate the underlying mechanisms and validate these findings in diverse populations.

Keywords:

Gut microbiota; Colon adenocarcinoma; Mendelian randomization

Cite the Article:

Wu ZY, Huang SK, Ye YY, Zheng WT, Chen HL, Hou XT, et al. The Causal Link Between Colon Adenocarcinoma and Gut Microbiota: A Bi-Directional Mendelian Randomization Study. World J Surg Surgical Res. 2024; 7: 1566..