Alteration of gut microbiota induced by DPP-4i treatment improves glucose homeostasisResearch in context
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
Affiliations
Xiaoyu Liao
Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Third Military Medical University, Chongqing, China
Lingyu Song
Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Third Military Medical University, Chongqing, China; Department of Gastroenterology, Affiliated Hospital of Guizhou Medical University, Guiyang, China
Benhua Zeng
Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China
Bingyao Liu
Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Third Military Medical University, Chongqing, China
Yuyang Qiu
Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Third Military Medical University, Chongqing, China
Hua Qu
Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Third Military Medical University, Chongqing, China
Yi Zheng
Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Third Military Medical University, Chongqing, China
Min Long
Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Third Military Medical University, Chongqing, China
Houdi Zhou
Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Third Military Medical University, Chongqing, China
Yuan Wang
Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Third Military Medical University, Chongqing, China
Yingxuan Du
Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Third Military Medical University, Chongqing, China
Jing Xu
Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Third Military Medical University, Chongqing, China
Rufei Shen
Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Third Military Medical University, Chongqing, China
Qiang Tong
Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Third Military Medical University, Chongqing, China
Leiqin Cai
Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Third Military Medical University, Chongqing, China
Xing Li
Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Third Military Medical University, Chongqing, China
Shaodong Guo
Department of Nutrition and Food Science, Texas A&M University, TX 77843, USA
Gangyi Yang
Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
Zhiming Zhu
Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing, China
Xiaoyun Pu
Department of Clinical Laboratory, Xinqiao Hospital, Third Military Medical University, Chongqing, China
Hong Wei
Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China; Correspondence to: H. Wei, Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400037, China.
Hongting Zheng
Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Third Military Medical University, Chongqing, China; Correspondence to: H. Zheng, Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital Third Military Medical University, Chongqing 400037, China.
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. Fund: This work was supported by grants from the National Natural Science Foundation of China (No. 81700757, No. 81471039, No. 81700714 and No. 81770434), the National Key R&D Program of China (No. 2017YFC1309602, No. 2016YFC1101100, No. 2017YFD0500503 and No. 2017YFD0501001), and the Natural Science Foundation of Chongqing (No. cstc2014jcyjjq10006, No. cstc2016jcyjA0093 and No. cstc2016jcyjA0518). Keywords: DPP-4i, Gut microbiota, Glucose tolerance, GF mice
