Qin Jiading, Zhang Ling, Zhang Guangcheng, Liao Weijie, Yu Li
Department of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Hematology Institution, Haoshi Cell Therapy Institute of Shenzhen University, Shenzhen University Medical School Shenzhen University Shenzhen China.
Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering Shenzhen University Medical School Shenzhen China.
Food Sci Nutr. 2025 Jun 23;13(6):e70456. doi: 10.1002/fsn3.70456. eCollection 2025 Jun.
Dietary factors may have a causative influence on acute myeloid leukemia (AML), a hematologic cancer known to be highly fatal. It is still mostly unknown whether causal mechanisms connect dietary exposures to AML, particularly through the gut microbiota and host metabolism. A two-sample Mendelian randomization (MR) analysis was conducted using genome-wide association study (GWAS) data to assess the causal effect of 20 routine dietary factors on AML. A two-step MR framework was employed to assess the mediating roles of gut microbiota and host metabolites. Sensitivity analyses, including inverse variance weighted (IVW), MR-Egger, and MR-PRESSO, were performed to ensure the robustness of results. Processed meat consumption was causally associated with an increased risk of AML (IVW OR = 15.111; 95% CI = 1.253-182.262; = 0.033). The gut microbiota-associated L-histidine degradation I pathway was identified as a pro-carcinogenic mediator, accounting for 19.5% of the effect. Conversely, host metabolites, including circulating glycerol levels and the free cholesterol-to-total lipids ratio in very large high-density lipoprotein (HDL), functioned as protective mediators. No substantial horizontal pleiotropy or heterogeneity was observed, thereby reinforcing the validity of these findings. This research offers a new understanding of the role of processed meat in the development of AML via the microbiota-metabolite axis and emphasizes possible metabolic compensatory pathways.
饮食因素可能对急性髓系白血病（AML）产生因果影响，AML是一种已知具有高度致命性的血液癌症。饮食暴露与AML之间是否存在因果机制，尤其是通过肠道微生物群和宿主代谢，目前仍大多未知。利用全基因组关联研究（GWAS）数据进行了两样本孟德尔随机化（MR）分析，以评估20种常规饮食因素对AML的因果效应。采用两步MR框架来评估肠道微生物群和宿主代谢物的中介作用。进行了敏感性分析，包括逆方差加权（IVW）、MR-Egger和MR-PRESSO，以确保结果的稳健性。加工肉类消费与AML风险增加存在因果关系（IVW OR = 15.111；95%CI = 1.253 - 182.262；P = 0.033）。肠道微生物群相关的L-组氨酸降解I途径被确定为一种促癌介质，占该效应的19.5%。相反，宿主代谢物，包括循环甘油水平和超大高密度脂蛋白（HDL）中的游离胆固醇与总脂质比率，起到了保护介质的作用。未观察到明显的水平多效性或异质性，从而加强了这些发现的有效性。本研究通过微生物群-代谢物轴对加工肉类在AML发生发展中的作用提供了新的认识，并强调了可能的代谢补偿途径。
