Jia Zixuan, Liu Xiufeng, Liao Wei
Intensive Care Unit, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Biotherapy Center/Melanoma and Sarcoma Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Microbiol Spectr. 2024 Aug 6;12(8):e0394823. doi: 10.1128/spectrum.03948-23. Epub 2024 Jul 11.
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 (OR = 3.7908, 95% CI: 1.4464-9.9350, = 0.01), (OR = 3.3295, 95% CI: 1.2794-8.6643, = 0.01), (OR = 2.6284, 95% CI: 1.0548-6.5498, = 0.04), and (OR = 2.5694, 95% CI: 1.0392-6.3526, = 0.04) were positively associated with chemotherapy efficacy using the IVW method. Conversely, (OR = 0.2283, 95% CI: 0.0699-0.7461, = 0.01) and (OR = 0.4953, 95% CI: 0.2443-1.0043, = 0.05) exhibited negative associations. WME demonstrated consistent results with IVW method only for (OR = 0.3343, 95% CI: 0.1298-0.8610, = 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 , 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 , 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.
新出现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，确定因果关系仍然很困难。本研究利用双向双样本孟德尔随机化（MR）分析，探讨肠道微生物群与化疗疗效之间的因果关系。利用来自MiBioGen联盟的全基因组关联研究（GWAS）数据来研究肠道微生物群，并利用IEU Open GWAS的数据来研究化疗疗效，我们采用基因变异作为工具变量（IVs）。应用了逆方差加权（IVW）方法、加权中位数估计器（WME）和MR-Egger回归方法，并进行了敏感性分析以确保稳健性。此外，我们还进行了化疗疗效与已识别的重要肠道微生物分类群之间的反向MR分析。结果表明，使用IVW方法时，（比值比=3.7908，95%置信区间：1.4464-9.9350，P=0.01）、（比值比=3.3295，95%置信区间：1.2794-8.6643，P=0.01）、（比值比=2.6284，95%置信区间：1.0548-6.5498，P=0.04）和（比值比=2.5694，95%置信区间：1.0392-6.3526，P=0.04）与化疗疗效呈正相关。相反，（比值比=0.2283，95%置信区间：0.0699-0.7461，P=）和（比值比=0.4953，95%置信区间：0.2443-1.0043，P=0.05）呈负相关。WME仅在（比值比=0.3343，95%置信区间：0.1298-0.8610，P=0.02）时与IVW方法得出的结果一致。未观察到显著的异质性或水平多效性。反向MR分析显示化疗对已识别的肠道微生物群没有显著的因果效应。本研究揭示了肠道微生物群，特别是[此处原文缺失具体微生物群名称]与化疗疗效之间的复杂关系，为完善癌症治疗策略提供了有价值的见解。重要性近年来，癌症治疗，特别是化疗方面的全球进展显著降低了死亡率。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。我们强调[此处原文缺失具体微生物群名称]作用的研究在阐明这种复杂的相互作用方面取得了关键进展。所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准度和改善患者预后的努力。此外，我们的发现有望用于个性化治疗干预，在不断发展的癌症治疗领域塑造更好的策略。
