新的证据强调了肠道微生物群与化疗疗效之间的复杂联系。然而，由于混杂因素，确定因果关系仍然难以实现。本研究利用双向两个样本孟德尔随机化 (MR) 分析，探讨肠道微生物群与化疗疗效之间的因果关系。利用 MiBioGen 联盟的肠道微生物群全基因组关联研究 (GWAS) 数据和 IEU Open GWAS 的化疗疗效数据，我们采用遗传变异作为工具变量 (IV)。采用逆方差加权（IVW）方法、加权中值估计（WME）和MR-Egger回归方法，并通过敏感性分析确保稳健性。此外，我们对化疗疗效进行了反向 MR 分析，并确定了重要的肠道微生物类群。结果表明，丁酸球菌属 (OR = 3.7908，95% CI：1.4464-9.9350，P = 0.01)、Dorea (OR = 3.3295，95% CI：1.2794-8.6643，P = 0.01)、Hungatella (OR = 2.6284，95) % CI：1.0548-6.5498，P = 0.04）和 Turicibacter（OR = 2.5694，95% CI：1.0392-6.3526，P = 0.04）与 IVW 方法的化疗疗效呈正相关。相反，紫单胞菌科（OR = 0.2283，95% CI：0.0699-0.7461，P = 0.01）和 Eggerthella 属（OR = 0.4953，95% CI：0.2443-1.0043，P = 0.05）表现出负相关。仅对于 Eggerthella 属，WME 与 IVW 方法的结果一致（OR = 0.3343，95% CI：0.1298-0.8610，P = 0.02）。没有观察到显着的异质性或水平多效性。反向磁共振分析显示化疗对已确定的肠道微生物群没有显着的因果影响。这项研究揭示了肠道微生物群（特别是埃格氏菌属）与化疗疗效之间的复杂关系，为完善癌症治疗策略提供了宝贵的见解。最近几年。然而，肠道微生物群与化疗疗效之间的相关性仍然难以捉摸。我们的研究强调了 Eggerthella 属的作用，代表了阐明这种复杂相互作用的关键进展。已确定的关联提供了潜在的治疗靶点，有助于全球提高治疗精度和改善患者预后的努力。此外，我们的研究结果有望实现个性化治疗干预，从而在不断发展的癌症治疗领域制定改进的策略。

Emerging evidence has underscored the complex link between gut microbiota and chemotherapy efficacy; however, establishing causality remains elusive due to confounding factors. This study, leveraging bidirectional two-sample Mendelian randomization (MR) analyses, explores the casual relationship between gut microbiota and chemotherapy efficacy. Utilizing genome-wide association study (GWAS) data from the MiBioGen consortium for gut microbiota and IEU Open GWAS for chemotherapy efficacy, we employed genetic variants as instrumental variables (IVs). The inverse variance weighted (IVW) method, weighted median estimator (WME), and MR-Egger regression method were applied, with sensitivity analyses ensuring robustness. Furthermore, we conducted reverse MR analyses between chemotherapy efficacy and identified significant gut microbial taxa. The results indicated that genus Butyricicoccus (OR = 3.7908, 95% CI: 1.4464-9.9350, P = 0.01), Dorea (OR = 3.3295, 95% CI: 1.2794-8.6643, P = 0.01), Hungatella (OR = 2.6284, 95% CI: 1.0548-6.5498, P = 0.04), and Turicibacter (OR = 2.5694, 95% CI: 1.0392-6.3526, P = 0.04) were positively associated with chemotherapy efficacy using the IVW method. Conversely, family Porphyromonadaceae (OR = 0.2283, 95% CI: 0.0699-0.7461, P = 0.01) and genus Eggerthella (OR = 0.4953, 95% CI: 0.2443-1.0043, P = 0.05) exhibited negative associations. WME demonstrated consistent results with IVW method only for genus Eggerthella (OR = 0.3343, 95% CI: 0.1298-0.8610, P = 0.02). No significant heterogeneity or horizontal pleiotropy was observed. Reverse MR analyses revealed no significant causal effect of chemotherapy on identified gut microbiota. This study sheds light on the intricate relationship between gut microbiota, with a particular emphasis on the genus Eggerthella, and chemotherapy efficacy, offering valuable insights for refining cancer treatment strategies.IMPORTANCEGlobal advancements in cancer treatment, particularly in chemotherapy, have notably decreased mortality rates in recent years. However, the correlation between gut microbiota and chemotherapy efficacy remains elusive. Our study, emphasizing the role of genus Eggerthella, represented a crucial advance in elucidating this intricate interplay. The identified associations offer potential therapeutic targets, contributing to global efforts for enhanced treatment precision and improved patient outcomes. Furthermore, our findings hold promise for personalized therapeutic interventions, shaping improved strategies in the ever-evolving landscape of cancer treatment.