基于TMA/FMO3/TMAO通路探讨肠道微生物组对脾失健运膏脂转输障碍的影响及机制

脾失健运膏脂转输障碍是血脂异常关键病机，而血脂异常是AS重要危险因素。近年来肠道微生物调控脂质代谢成为基础和临床关注的热点，最新研究发现，肠道微生物主要通过调控TMA/FMO3/TMAO通路干预脂质代谢，特别是影响RCT途径和HDL质量。课题组前期研究证实脾失健运膏脂转输障碍导致RCT受阻，HDL亚类异常，FMO3及dyHDL标志载脂蛋白SAA表达增强，提示肠道微生物改变可能与脾失健运膏脂转输障碍密切关联。本课题拟以脾虚高脂血症人群及模型大鼠为研究对象，以肠道微生物组及其驱动的TMA/FMO3/TMAO通路为切入点，围绕dyHDL和RCT途径，利用宏基因组测序、LC-MS等技术，初步阐明脾虚状态下肠道微生物调控膏脂转输的关键途径、环节及分子机理，并揭示健脾化浊法的效应机制。丰富“脾主运化”理论科学内涵，并为挖掘以肠道微生物组为有效靶点防治AS相关疾病健脾降脂中药提供新的研究策略和实验依据。

The disorder of the spleen and Gaozhi transportation and transformation dysfunction is the key pathogenesis of dyslipidemia. And dyslipidemia is an important risk factor for AS. In recent years, gut microbes regulating lipid metabolism has become the hot topic in basic and clinical. The latest study found that gut microbes mainly through regulating the TMA/FMO3/TMAO pathway to intervene the lipid metabolism, in particular, affect the RCT pathway and HDL quality. The preliminary study of the research group confirmed that the disorder of the spleen and Gaozhi transportation and transformation dysfunction could result in the RCT blocked, HDL subclass abnormalities, the expressions of FMO3 and dyHDL marker apolipoprotein SAA increased, suggesting that changes in the gut microbiome may be closely related to the disorder of the spleen and Gaozhi transportation and transformation dysfunction. This project is conducting the spleen deficiency hyperlipidemia patients and model rats as the research object, using the TMA/FMO3/TMAO pathway as the starting point, centreing on the dyHDL and RCT pathway, and taking advantages of the techniques of macro genome sequencing and LC-MS, preliminary elaboration the key pathways, links and molecular mechanisms of the gut microbes regulation of Gaozhi transportation and transformation in the spleen deficiency state. And reveal the effect mechanism of invigorating spleen to dissolve turbidity, enrich the scientific connotation of the theory of “spleen governing transportation and transformation”, and provide a new research strategy and experimental basis for digging the invigorating spleen to dissolve turbidity traditional Chinese medicine which is regarding the gut microbiome as a effective target, for preventing and treating AS related diseases.