pp 1–9 | Cite as

Response of gut microbiota in type 2 diabetes to hypoglycemic agents

  • Fanghua Zhang
  • Meng Wang
  • Junjie Yang
  • Qian Xu
  • Cheng Liang
  • Bin Chen
  • Jiaming Zhang
  • Ying Yang
  • Huiling Wang
  • Yongfang Shang
  • Ye Wang
  • Xiaofeng Mu
  • Dequan Zhu
  • Chunling Zhang
  • Minxiu YaoEmail author
  • Lei Zhang
Original Article



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.


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.


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.


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.


Microbiota Type 2 diabetes Metformin Insulin α-Glucosidase inhibitors. 



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).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

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.

Informed consent

All the subjects signed informed consent beforehand and belonged to the same geographical area. Data were collected by using a standardized questionnaire, including basic information, medical history, and examination results.

Supplementary material

12020_2019_2041_MOESM1_ESM.xlsx (55 kb)
Supplementary Table S1
12020_2019_2041_MOESM2_ESM.xlsx (49 kb)
Supplementary Table S2


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Fanghua Zhang
    • 1
    • 2
  • Meng Wang
    • 3
  • Junjie Yang
    • 4
    • 5
  • Qian Xu
    • 1
  • Cheng Liang
    • 6
  • Bin Chen
    • 7
  • Jiaming Zhang
    • 8
  • Ying Yang
    • 1
  • Huiling Wang
    • 1
  • Yongfang Shang
    • 1
  • Ye Wang
    • 2
    • 9
  • Xiaofeng Mu
    • 2
    • 9
  • Dequan Zhu
    • 10
  • Chunling Zhang
    • 2
  • Minxiu Yao
    • 1
    • 2
    Email author
  • Lei Zhang
    • 7
  1. 1.Department of EndocrinologyThe Affiliated Central Hospital of Qingdao UniversityQingdaoChina
  2. 2.Qingdao Human Microbiome CenterThe Affiliated Central Hospital of Qingdao UniversityQingdaoChina
  3. 3.College of Marine Life SciencesOcean University of ChinaQingdaoChina
  4. 4.College of Life ScienceQilu Normal UniversityJinanChina
  5. 5.Shandong Children’s Microbiome CenterQilu Children’s Hospital of Shandong UniversityJinanChina
  6. 6.School of Information Science and EngineeringShandong Normal UniversityJinanChina
  7. 7.Beijing Advanced Innovation Center for Big Data-Based Precision MedicineBeihang UniversityBeijingChina
  8. 8.Shandong Institutes for Food and Drug ControlJinanChina
  9. 9.Clinical Laboratory and Core Research LaboratoryThe Affiliated Central Hospital of Qingdao UniversityQingdaoChina
  10. 10.Microbiological LaboratoryLin Yi People’s HospitalLinyiChina

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