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Response of gut microbiota in type 2 diabetes to hypoglycemic agents

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Abstract

Purpose

Accumulated evidence has indicated that the gut microbiome affected the pharmacology of anti-diabetic agents, and their metabolic products induced by the agents transformed the structure of gastrointestinal microbiota in return. However, the studies around heredity, ethnicity, or living condition, referring to human microbiome were mostly represented by an occidental pattern partial and rare studies that focused on the effect of several first-line hypoglycemic agents on the gut flora in a single medical center. Therefore, we aimed to explore the interaction between gut microbiome and type 2 diabetes (T2D) or hypoglycemics in Chinese population.

Methods

A total of 130 T2D patients with a specific hypoglycemic treatment and 50 healthy volunteers were enrolled in this study. Gut microbiome compositons were analyzed by 16S ribosomal RNA gene-based sequencing protocol.

Results

Hypoglycemic agents contributed to the alteration of specific species in gut bacteria rather than its total diversity. Metformin increased the abundance of Spirochaete, Turicibacter, and Fusobacterium. Insulin also increased Fusobacterium, and α-glucosidase inhibitors (α-GIs) contributed to the plentitude of Bifidobacterium and Lactobacillus. Both metformin and insulin improved taurine and hypotaurine metabolism, and α-GI promoted several amino acid pathways. Although the community of gut microbiota with metformin and insulin showed similarity, significant differences were available in each diabetic group with hypoglycemia.

Conclusions

Gut microbiota is significantly associated with anti-diabetic agents. The gut microbiome and metabolism have shown respective characteristics in different T2D groups, which were also significantly different from the healthy group. This study provides some new insights for identification and exploration of the pathogenesis of T2D.

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Funding

This project has been supported by the National Natural Science Foundation of China under contract no. 31471202 (to L.Z.) and no. 81670822 (to Y.W.); the Shandong Provincial Key Research and Development Program under contract no. 2016YYSP009 (to L.Z.); Weihai Technique Extension Project under contract no. 2016GNS023 (to L.Z.); Qingdao Key Research Project No. 17-3-3-10-nsh (to C.Z.). L.Z. is also supported by the Taishan Scholars Program of Shandong Province (no. tshw20120206).

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Author notes

  1. These authors contributed equally: Fanghua Zhang, Meng Wang, Junjie Yang

Authors and Affiliations

  1. Department of Endocrinology, The Affiliated Central Hospital of Qingdao University, Qingdao, Shandong Province, China

    Fanghua Zhang, Qian Xu, Ying Yang, Huiling Wang, Yongfang Shang & Minxiu Yao

  2. Qingdao Human Microbiome Center, The Affiliated Central Hospital of Qingdao University, Qingdao, Shandong Province, China

    Fanghua Zhang, Ye Wang, Xiaofeng Mu, Chunling Zhang & Minxiu Yao

  3. College of Marine Life Sciences, Ocean University of China, Qingdao, Shandong Province, China

    Meng Wang

  4. College of Life Science, Qilu Normal University, Jinan, Shandong Province, China

    Junjie Yang

  5. Shandong Children’s Microbiome Center, Qilu Children’s Hospital of Shandong University, Jinan, Shandong Province, 250022, China

    Junjie Yang

  6. School of Information Science and Engineering, Shandong Normal University, Jinan, Shandong Province, China

    Cheng Liang

  7. Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing, China

    Bin Chen & Lei Zhang

  8. Shandong Institutes for Food and Drug Control, Jinan, Shandong Province, China

    Jiaming Zhang

  9. Clinical Laboratory and Core Research Laboratory, The Affiliated Central Hospital of Qingdao University, Qingdao, Shandong Province, China

    Ye Wang & Xiaofeng Mu

  10. Microbiological Laboratory, Lin Yi People’s Hospital, Linyi, Shandong Province, China

    Dequan Zhu

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  1. Fanghua Zhang
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Correspondence to Minxiu Yao or Lei Zhang.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Research involving human participants and/or animals: this article does not contain any studies with animals performed by any of the authors.

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Zhang, F., Wang, M., Yang, J. et al. Response of gut microbiota in type 2 diabetes to hypoglycemic agents. Endocrine 66, 485–493 (2019). https://doi.org/10.1007/s12020-019-02041-5

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