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Alteration of gut microbiota induced by DPP-4i treatment improves glucose homeostasis DOI: 10.1016/j.ebiom.2019.03.057 Abstract & Authors 展开 Abstract:
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 α-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 α-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 HFD were rescued by DPP-4i. FMT 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.
First Authors:
Xiaoyu Liao,Lingyu Song,Benhua Zeng Correspondence:
Hong Wei,Hongting Zheng All Authors:
Xiaoyu Liao,Lingyu Song,Benhua Zeng,Bingyao Liu,Yuyang Qiu,Hua Qu,Yi Zheng,Min Long,Houdi Zhou,Yuan Wang,Yingxuan Du,Jing Xu,Rufei Shen,Qiang Tong,Leiqin Cai,Xing Li,Shaodong Guo,Gangyi Yang,Zhiming Zhu,Xiaoyun Pu,Hong Wei,Hongting Zheng Article2019-03-26
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