糖尿病会改变肠道CYP3A和P-gp，但作用机制尚不明确。肠道菌群与糖尿病的发生发展密切相关，并且有研究表明肠道菌群对某些代谢酶和转运体具有调控作用。由此我们推测肠道菌可能参与糖尿病对肠道CYP3A和P-gp的调控过程。本项目拟探索糖尿病、肠道菌群、肠道代谢酶和转运体以及药代动力学之间的联系。重点考察糖尿病动物和患者的肠道菌群和肠道CYP3A和P-gp的区域性变化，以及这些变化的种属差异和性别差异，并研究肠道菌参与糖尿病改变肠道代谢酶和转运体的作用机制；分析抗生素加替沙星如何通过改变肠道菌群影响糖尿病；此外通过同时比较底物药物硝苯地平、洛伐他汀在糖尿病动物和人体内的口服药代动力学变化，考察其种属差异性并进行转化医学的相关研究。其成果有助于阐明肠道菌对糖尿病的影响，糖尿病改变CYP3A和P-gp的作用机制以及底物药物在糖尿病状态下的药代动力学特征，对于指导糖尿病患者临床合理用药具有重要意义。

Diabetes could change the function and expression of intestinal CYP3A and P-glycoprotein (P-gp), but the mechanism is still unknown. The gut microbiota is associated with the onset and development of diabetes, and resent researches showed that gut microbiota could also regulate some metabolizing enzymes and transporters. This project is going to explore the relationship among diabetes, gut microbiota, intestinal metabolizing enzyme and transporter and pharmacokinetics of drugs. This research will emphasis on the regional changes of gut microbiota and intestinal CYP3A and P-gp of diabetic animals and patients, the species and sex difference of these changes will also be included. The mechanism of the regulation of intestinal enzyme and transporter by diabetes in which gut microbiota were taken part will be investigated. How does the antibiotic gatifloxacin influence the diabetes through the interaction with gut microbiota will be explored. Besides, the changes of oral pharmacokinetics of nifedipine and lovastatin will be compared in diabetic animals and patients simultaneously to judge whether the species difference of these changes is exist and the research about translational medicine will be studied. The findings could help elucidate the influence of gut microbiota on diabetes, the mechanism of the regulation of intestinal CYP3A and P-gp by diabetes, and the pharmacokinetic changes of the substrate drugs under diabetes states. The results may also help to give diabetic patients guidelines for drug use in clinic.