Wu Binxiong, Xu Yuntian, Tang Miaomiao, Jiang Yingtong, Zhang Ting, Huang Lei, Wang Shuyang, Hu Yanhui, Zhou Kun, Zhang Xiaoling, Chen Minjian
Department of Hygienic Analysis and Detection, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Toxics. 2023 Dec 22;12(1):14. doi: 10.3390/toxics12010014.
Metabolism underlies the pathogenesis of acute myeloid leukemia (AML) and can be influenced by gut microbiota. However, the specific metabolic changes in different tissues and the role of gut microbiota in AML remain unclear. In this study, we analyzed the metabolome differences in blood samples from patients with AML and healthy controls using UPLC-Q-Exactive. Additionally, we examined the serum, liver, and fecal metabolome of AML model mice and control mice using UPLC-Q-Exactive. The gut microbiota of the mice were analyzed using 16S rRNA sequencing. Our UPLC-MS analysis revealed significant differences in metabolites between the AML and control groups in multiple tissue samples. Through cross-species validation in humans and animals, as well as reverse validation of Celastrol, we discovered that the Carnosine-Histidine metabolic pathway may play a potential role in the occurrence and progression of AML. Furthermore, our analysis of gut microbiota showed no significant diversity changes, but we observed a significant negative correlation between the key metabolite Carnosine and and . In conclusion, the Carnosine-Histidine metabolic pathway influences the occurrence and progression of AML, while the gut microbiota might play a role in this process.
代谢是急性髓系白血病（AML）发病机制的基础，并且可能受到肠道微生物群的影响。然而，不同组织中的具体代谢变化以及肠道微生物群在AML中的作用仍不清楚。在本研究中，我们使用超高效液相色谱-四极杆-静电场轨道阱高分辨质谱仪（UPLC-Q-Exactive）分析了AML患者和健康对照者血液样本中的代谢组差异。此外，我们还使用UPLC-Q-Exactive检测了AML模型小鼠和对照小鼠的血清、肝脏和粪便代谢组。使用16S rRNA测序分析了小鼠的肠道微生物群。我们的UPLC-MS分析揭示了多个组织样本中AML组和对照组之间代谢物的显著差异。通过在人和动物中的跨物种验证以及对雷公藤红素的反向验证，我们发现肌肽-组氨酸代谢途径可能在AML的发生和发展中发挥潜在作用。此外，我们对肠道微生物群的分析显示没有显著的多样性变化，但我们观察到关键代谢物肌肽与[此处原文缺失部分内容]之间存在显著的负相关。总之，肌肽-组氨酸代谢途径影响AML的发生和发展，而肠道微生物群可能在此过程中发挥作用。
