Alteration of gut microbiota induced by DPP-4i treatment improves glucose homeostasis
Alteration of gut microbiota induced by DPP-4i treatment improves glucose homeostasis
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DPP-4i 治疗引起的肠道微生物群改变可改善葡萄糖稳态
DOI：
10.1016/j.ebiom.2019.03.057
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发表时间：
2019-06-01
期刊：
影响因子：
11.1
通讯作者：
Zheng, Hongting
中科院分区：
文献类型：
--
作者：
Liao, Xiaoyu;Song, Lingyu;Zheng, Hongting
背景：越来越多的证据表明，肠道菌群参与代谢性疾病的发生和发展。然而，关于常用的抗糖尿病药物对肠道微生物群的影响知之甚少。本研究探讨二肽基肽酶-4抑制剂（DPP-4 i）和α-葡萄糖苷酶抑制剂在调节肠道菌群中的作用。方法：采用16 S-rDNA测序技术分析DPP-4 i和阿卡波糖对高脂饮食（HFD）小鼠肠道菌群的影响。进行了从2型糖尿病患者到无菌小鼠的粪便微生物群移植（FMT），以研究改变的微生物群对药物抗糖尿病作用的贡献。通过非靶向和靶向GC-MS systems.Findings分析粪便代谢组学：虽然DPP-4 i和α-葡萄糖苷酶抑制剂都改变了肠道微生物组成，但只有DPP-4 i的微生物组调节有助于其降血糖作用。DPP-4 i对HID诱导的68.6%属的变化有挽救作用。[MT显示DPP-4 i改变的微生物组改善了定植小鼠的葡萄糖耐量，而阿卡波糖没有。而且。DPP-4 i增加了拟杆菌的丰度，也促进了肠道微生物组的功能转变，特别是增加了琥珀酸的产量。解释：我们的研究结果证明了DPP-4 i对肠道微生物群的重要影响，揭示了一种新的降血糖机制及其额外的益处。此外，调节微生物组成，以及微生物组变化引起的功能转变，可能是改善葡萄糖稳态的潜在策略。(C)2019作者由爱思唯尔公司出版
Background: Increasing evidence indicates that the gut microbiota contributes to the occurrence and development of metabolic diseases. However, little is known about the effects of commonly used antidiabetic agents on the gut microbiota. In this study, we investigated the roles of dipeptidyl peptidase-4 inhibitors (DPP-4i) and alpha-glucosidase inhibitor in modulating the gut microbiota.Methods: 16S-rDNA sequencing was performed to analyse the effects of DPP-4i and acarbose on the gut microbiota in mice fed a high-fat diet (HFD). Fecal microbiota transplantation (FMT) from type 2 diabetes patients to germ-free mice was performed to investigate the contribution of the altered microbiome to antidiabetic effects of the drugs. Fecal metabolomics was also analysed by untargeted and targeted GC-MS systems.Findings: Although DPP-4i and a-glucosidase inhibitor both altered the gut microbial composition, only the microbiome modulation of DPP-4i contributed to its hypoglycemic effect. Specifically, the changes of 68.6% genera induced by HID were rescued by DPP-4i. [MT showed that the DPP-4i-altered microbiome improved glucose tolerance in colonized mice, while acarbose did not. Moreover. DPP-4i increased the abundance of Bacteroidetes, and also promoted a functional shift in the gut microbiome, especially increasing the production of succinate.Interpretation: Our findings demonstrate an important effect of DPP-4i on the gut microbiota, revealing a new hypoglycemic mechanism and an additional benefit of it. Furthermore, modulating the microbial composition, and the functional shift arising from changes in the microbiome, might be a potential strategy for improving glucose homeostasis. (C) 2019 The Authors. Published by Elsevier B.V.