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Alteration of Gut Microbiota Induced by DPP-4i Treatment Improves Glucose Homeostasis

41 Pages Posted: 17 Nov 2018

See all articles by Xiaoyu Liao

Xiaoyu Liao

Third Military Medical University

Lingyu Song

Third Military Medical University

Benhua Zeng

Third Military Medical University

Yuyang Qiu

Third Military Medical University

Bingyao Liu

Third Military Medical University

Hua Qu

Third Military Medical University

Yi Zheng

Third Military Medical University

Min Long

Third Military Medical University

Houdi Zhou

Third Military Medical University

Yuan Wang

Third Military Medical University

Yingxuan Du

Third Military Medical University

Jing Xu

Third Military Medical University

Rufei Shen

Third Military Medical University

Qiang Tong

Third Military Medical University

Leiqin Cai

Third Military Medical University

Xing Li

Third Military Medical University

Shaodong Guo

Texas A&M University

Gangyi Yang

Chongqing University

Zhiming Zhu

Third Military Medical University

Xiaoyun Pu

Third Military Medical University

Hong Wei

HuaZhong Agricultural University - The Engineering Technology Research Center for Germ-free and Genome-editing Animal; HuaZhong Agricultural University - Key Laboratory of Swine Genetics and Breeding of the Ministry of Agriculture

Hongting Zheng

Government of the People's Republic of China - Department of Endocrinology

More...

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 rRNA sequencing was performed to analyze 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 diabetic patients to germ-free mice was conducted to investigate the contribution of the altered microbiome to antidiabetic effects of the drugs. Fecal metabolomics were also analyzed 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 conventionalized mice, while acarbose did not. Moreover, DPP-4i reduced the ratio of Firmicutes to Bacteroidetes, predominantly by increasing the abundance of Bacteroidetes. It also promoted the functional shift in the gut microbiome, especially the increased production of succinate.  

Interpretation: Our findings demonstrate a novel effect of DPP-4i on the gut microbiota, revealing a new hypoglycemic mechanism and additional benefit for it. Furthermore, modulating the ratio of Firmicutes to Bacteroidetes, and the functional shift arising from changes in the microbiome, might be a potential strategy for improving glucose homeostasis.  

Clinical Trial Number: Complete clinical trial registration is deposited in the Chinese Clinical Trials Registry (http://www.chictr.org.cn/index.aspx), and the registration number is ChiCTR-OPC-17010757.

Funding Statement: 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 Project of Chongqing (No. cstc2014jcyjjq10006, No. cstc2016jcyjA0093 and No. cstc2016jcyjA0518).

Declaration of Interests: The authors disclose no conflicts interest.

Ethics Approval Statement: Informed written consent was obtained from all participants. The experiment was approved by the Ethics Committee of Xinqiao Hospital of the Third Military Medical University.

Keywords: DPP-4i; Microbiome; Glucose Tolerance; GF Mice

Suggested Citation

Liao, Xiaoyu and Song, Lingyu and Zeng, Benhua and Qiu, Yuyang and Liu, Bingyao and Qu, Hua and Zheng, Yi and Long, Min and Zhou, Houdi and Wang, Yuan and Du, Yingxuan and Xu, Jing and Shen, Rufei and Tong, Qiang and Cai, Leiqin and Li, Xing and Guo, Shaodong and Yang, Gangyi and Zhu, Zhiming and Pu, Xiaoyun and Wei, Hong and Zheng, Hongting, Alteration of Gut Microbiota Induced by DPP-4i Treatment Improves Glucose Homeostasis (November 14, 2018). Available at SSRN: https://ssrn.com/abstract=3284852

Xiaoyu Liao

Third Military Medical University

Chongqing
China

Lingyu Song

Third Military Medical University

Chongqing
China

Benhua Zeng

Third Military Medical University

Chongqing
China

Yuyang Qiu

Third Military Medical University

Chongqing
China

Bingyao Liu

Third Military Medical University

Chongqing
China

Hua Qu

Third Military Medical University

Chongqing
China

Yi Zheng

Third Military Medical University

Chongqing
China

Min Long

Third Military Medical University

Chongqing
China

Houdi Zhou

Third Military Medical University

Chongqing
China

Yuan Wang

Third Military Medical University

Chongqing
China

Yingxuan Du

Third Military Medical University

Chongqing
China

Jing Xu

Third Military Medical University

Chongqing
China

Rufei Shen

Third Military Medical University

Chongqing
China

Qiang Tong

Third Military Medical University

Chongqing
China

Leiqin Cai

Third Military Medical University

Chongqing
China

Xing Li

Third Military Medical University

Chongqing
China

Shaodong Guo

Texas A&M University

Langford Building A
798 Ross St.
College Station, TX 77843-3137
United States

Gangyi Yang

Chongqing University

Shazheng Str 174, Shapingba District
Chongqing 400044, Chongqing 400030
China

Zhiming Zhu

Third Military Medical University

Chongqing
China

Xiaoyun Pu

Third Military Medical University

Chongqing
China

Hong Wei

HuaZhong Agricultural University - The Engineering Technology Research Center for Germ-free and Genome-editing Animal ( email )

Wuhan, 430070
China

HuaZhong Agricultural University - Key Laboratory of Swine Genetics and Breeding of the Ministry of Agriculture ( email )

Wuhan, 430070
China

Hongting Zheng (Contact Author)

Government of the People's Republic of China - Department of Endocrinology ( email )

Chongqing, 400037
China

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