肠道微生物作为肥胖发展的机体环境因素之一日益受到研究者的关注，但宿主在肥胖过程中调节肠道菌群的机制尚不清楚。本项目基于目前Paneth细胞（PC）抗菌肽及其内质网（ER）应激与肥胖和肠道菌群方面的研究，采用本项目组已建立的检测肠道菌群方法，拟用高脂日粮诱导正常小鼠产生肥胖，在肥胖发展过程中测定小鼠的PC ER应激、抗菌肽表达及肠道菌群数量，在小鼠上论证高能日粮诱导肥胖可能导致PC ER应激，并造成其分泌的抗菌肽表达减少的假说，初步判定PC ER应激可能与肠道菌群的关系；继而在肥胖小鼠中使用ER应激调节物，以弄清PC ER应激及其抗菌肽表达变化是否为肥胖宿主调节肠道菌群的途径之一；最后用益生素饲喂肥胖小鼠改变肠道菌群，并考察对PC ER应激及其抗菌肽表达的影响，揭示其与肠道菌群的关系。开展本研究可进一步认识调节肠道菌群和肥胖发展的潜在机制，并为深入开展肥胖控制研究提供相关科学依据。

The gut microbiota has attracted much attention as an environmental factor involved in the development of obesity, but less is known about host factors that may regulate the composition of this ecosystem. This research based on the studies about Paneth cell (PC) antimicrobial peptides (AMPs), endoplasmic reticulum (ER) stress, obesity and gut bacteria. Firstly, using our method for detecting gut bacteria, we plan to induce the nomal mice producing obesity, determine PC ER stress, PC AMPs expression and gut microbiota quantity during the development of obesity, demonstrate hypothesis that obesity may result in PC ER stress and decreasing expression of PC AMPs in the mice, and assess initially the possible relationship of PC ER stress and gut bacteria. Secondly, supplying ER stress regulator to obese mice to investigate whether PC ER stress and its AMPs expression changes may be one of the pathways through which obese host regulate gut microbiota. Finally, regulation of gut flora in obese mice using prebiotics to evaluate the effect of gut bacteria on PC ER stress and its AMPs expression, and reveal their relationship. This study may further know about the underlying mechanisms of regulating gut bacteria and development of obesity, and provide reference to control of obesity.