Supplementary table, figures and code File

Microbiome dysbiosis has been linked to creating a favorable environment for cancer development by disrupting immune responses, altering hormone metabolism, and affecting cell cycle regulation and apoptosis. Notably, studies have explored the connection between the gut microbiome and EC. Our study employs a Mendelian randomization (MR) approach, utilizing genetic variants as instrumental variables, to investigate the causal associations between gut microbiota, plasma metabolites, and EC. Our findings revealed 16 mediation pathways involving 4 microbial species and 14 plasma metabolites, highlighting potential connections between gut microbiota and EC, with some metabolites such as Carboxyethyl-GABA and Glycodeoxycholate 3-sulfate mediating the effects of gut microbiota on EC.Our research provides novel insights into the causal relationship between the gut microbiota, plasma metabolites, and EC, indicating potential targets for intervention in the disease. We are convinced that these discoveries hold substantial relevance for the domain of gynecological oncology research and clinical practice, potentially exerting a significant impact on the prevention and therapeutic strategies for EC.

菌群失调（Microbiome dysbiosis）可通过破坏免疫应答、改变激素代谢、影响细胞周期调控与细胞凋亡，为癌症发生营造适宜的微环境。尤为值得关注的是，已有诸多研究探讨了肠道菌群与子宫内膜癌（Endometrial Cancer, EC）之间的关联。本研究采用孟德尔随机化（Mendelian randomization, MR）方法，以遗传变异作为工具变量（instrumental variables），探究肠道菌群、血浆代谢物与EC之间的因果关联。本研究结果共揭示了16条介导通路，涉及4种微生物菌种与14种血浆代谢物，凸显了肠道菌群与EC之间的潜在联系；其中羧乙基γ-氨基丁酸（Carboxyethyl-GABA）、甘氨脱氧胆酸3-硫酸盐（Glycodeoxycholate 3-sulfate）等代谢物可介导肠道菌群对EC的致病作用。本研究为肠道菌群、血浆代谢物与EC之间的因果关系提供了全新的研究视角，并指明了该疾病的潜在干预靶点。我们坚信，上述发现与妇科肿瘤学研究及临床实践具有高度相关性，有望对EC的预防与治疗策略产生重要影响。