Gut microbiota influences colorectal cancer through immune cell interactions: a Mendelian randomization study

• DOI: 10.1007/s12672-025-02486-3
• Publication Date: 2025-05-13T05:05:49Z
• Authors: Linyi Zheng; Yuqiang Li; Cenap Güngör; Heming Ge
• Keywords: Mendelian Randomization; Genome-wide Association Study

Abstract Background Colorectal cancer (CRC) is the most prevalent malignant tumor of digestive system globally, posing a significant threat to human health and quality life. Recent studies have established associations between gut microbiota immune cells with CRC; however, mechanisms by which influence development progression CRC through mediators remain poorly understood. Methods We conducted two-sample, bidirectional Mendelian randomization analysis. utilized 731 cell types 473 microbial species along colorectal statistics from published summary genome-wide association (GWAS).The analysis employed several methodologies, including inverse variance-weighted (IVW) analysis, MR-Egger regression, weighted median method, both simple model approaches.Sensitivity analyses were performed confirm reliability results, reverse was used assess overall impact on cells. Results Our findings suggest causal relationship involving nine immunophenotypes five specific taxa CRC. Notably, microbes Alloprevotella Holdemania, CD3 CD28- CD8br CD4 + T cells, demonstrated Mediation revealed that mediated mediation effect 6.48%. Additionally, Holdemania found mediate its CD8br, exhibiting 9.29%. Reverse did not indicate any or microbiota. Two-sided sensitivity no evidence heterogeneity horizontal pleiotropy in our findings. Conclusions This comprehensive study enhances understanding affects interactions. Further investigations are warranted unravel underlying linking microbiota, cancer.