PDF(Pubmed)
Abstract：
The role of the gut microbiota and its interplay with host metabolic health, particularly in the context of type 2 diabetes mellitus (T2DM) management, is garnering increasing attention. Dipeptidyl peptidase 4 (DPP4) inhibitors, commonly known as gliptins, constitute a class of drugs extensively used in T2DM treatment. However, their potential interactions with gut microbiota remain poorly understood. In this study, we employed computational methodologies to investigate the binding affinities of various gliptins to DPP4-like homologs produced by intestinal bacteria. The 3D structures of DPP4 homologs from gut microbiota species, including Segatella copri, Phocaeicola vulgatus, Bacteroides uniformis, Parabacteroides merdae, and Alistipes sp., were predicted using computational modeling techniques. Subsequently, molecular dynamics simulations were conducted for 200 ns to ensure the stability of the predicted structures. Stable structures were then utilized to predict the binding interactions with known gliptins through molecular docking algorithms. Our results revealed binding similarities of gliptins toward bacterial DPP4 homologs compared to human DPP4. Specifically, certain gliptins exhibited similar binding scores to bacterial DPP4 homologs as they did with human DPP4, suggesting a potential interaction of these drugs with gut microbiota. These findings could help in understanding the interplay between gliptins and gut microbiota DPP4 homologs, considering the intricate relationship between the host metabolism and microbial communities in the gut.
摘要：
肠道微生物群的作用及其与宿主代谢健康的相互作用，特别是在2型糖尿病（T2DM）管理的背景下，正在引起越来越多的关注。二肽基肽酶4（DPP4）抑制剂，通常被称为gliptins，构成了一类广泛用于T2DM治疗的药物。然而,它们与肠道微生物群的潜在相互作用仍然知之甚少.在这项研究中,我们采用计算方法研究了各种gliptin与肠道细菌产生的DPP4样同源物的结合亲和力.来自肠道微生物群物种的DPP4同源物的3D结构，包括SegatellaCopri,Pocaeicolavulgatus，均匀拟杆菌,Merdae副杆菌,和Alistipessp.,使用计算建模技术进行预测。随后，分子动力学模拟进行了200ns，以确保预测结构的稳定性。然后利用稳定结构通过分子对接算法预测与已知格列汀的结合相互作用。我们的结果揭示了与人DPP4相比，格列汀与细菌DPP4同源物的结合相似性。具体来说,某些gliptins对细菌DPP4同源物的结合评分与人类DPP4相似,提示这些药物与肠道微生物群存在潜在的相互作用.这些发现可能有助于理解gliptins和肠道微生物群DPP4同源物之间的相互作用。考虑到宿主代谢和肠道微生物群落之间的复杂关系。
