骨髓微环境免疫失衡是急性髓性白血病(AML)发病重要原因。新近证明肠道菌群调控骨髓造血和免疫功能。我们发现AML中存在肠道菌群及骨髓Th细胞免疫网络失衡，二者显著相关，认为“肠-骨髓轴”在AML发病中发挥重要作用。拟在系统生物学框架内，构建AML患者肠道菌群/代谢产物及骨髓Th细胞的贝叶斯网络，明确“肠道菌群-代谢产物-骨髓Th免疫”因果关系及关键节点；体外利用AML肠道菌群提取物/代谢产物作用于CD4+T或AML细胞，探究其对Th免疫及AML细胞作用机制。利用粪便菌群移植(FMT)，建立人源肠道菌群或鼠源FMT的AML小鼠，抗生素破坏肠道菌群及恢复后，检测小鼠AML发病、代谢及骨髓Th免疫变化；对小鼠进行菌体成分/代谢产物及Th细胞干预，观察对骨髓Th免疫失衡逆转及对AML小鼠生存影响，以期揭示肠道菌群通过“肠-骨髓轴”改变骨髓Th免疫网络调控AML作用机制，为AML靶向治疗提供借鉴。

Immunological deregulation in bone marrow microenvironment is the main reason for acute myeloid leukemia (AML). Gut microbiota has been recently proved to be vital in regulating the hematopoiesis and immunology in bone marrow environment. Our previous study has confirmed dysbiotic gut microbiota and imbalanced bone marrow Th immunological network in AML patients, and they are correlated significantly. Therefore, we speculate that “gut-bone marrow axis” plays important roles in the development of AML. Under the framework of systems biology and using experiments, we will construct the Bayesian network of gut microbiota/metabolites and Th subsets variation of AML patients, and clarify their association and key cells/molecules in “gut microbiota-metabolites-bone marrow Th immunology”. After treating CD4+ naïve T cells or AML cells with gut microbiota abstracts or metabolites, we will investigate their regulatory mechanism on Th immunological network, and clarify their effects on biological behavior of AML cells. Using the technique of fecal microbiota transplantation (FMT), we will establish AML mouse models transplanted with human gut microbiota or control mouse gut microbiota, or deplete gut microbiota with antibiotics and rescue it, then monitor the leukemia development, metobolites and Th immunological network in vivo. Furthermore, we will study the effects and mechanisms on AML mice survival and reversing imbalanced Th immunological network after applying gut microbiota abstracts/metabolites or interfering Th cells. Our project will demonstrate the detailed regulating effects and mechanisms of gut microbiota on immunological network via “gut-bone marrow axis” in AML, and provide strategy for AML targeting therapy.