Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2021; 27(8): 708-724
Published online Feb 28, 2021. doi: 10.3748/wjg.v27.i8.708
Effect of berberine on hyperglycaemia and gut microbiota composition in type 2 diabetic Goto-Kakizaki rats
Jin-Dong Zhao, Yan Li, Min Sun, Chan-Juan Yu, Jia-Yun Li, Si-Hai Wang, Di Yang, Cheng-Lin Guo, Xue Du, Wen-Jin Zhang, Ruo-Dong Cheng, Xiao-Chuan Diao, Zhao-Hui Fang
Jin-Dong Zhao, Chan-Juan Yu, Jia-Yun Li, Si-Hai Wang, Di Yang, Cheng-Lin Guo, Xue Du, Wen-Jin Zhang, Ruo-Dong Cheng, Xiao-Chuan Diao, Zhao-Hui Fang, Department of Endocrinology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, Anhui Province, China
Yan Li, Department of Infectious Diseases, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, Anhui Province, China
Min Sun, School of Life Sciences, Anhui University, Hefei 230039, Anhui Province, China
Author contributions: Zhao JD, Li Y and Fang ZH designed the study and wrote the manuscript; Sun M, Yu CJ, Li JY, Diao XC, Guo CL, Yang D, Du X, and Zhang WJ conducted the experiments; Wang SH and Cheng RD helped complete the data analysis and provided language modification; all authors read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81603574 and No. 81774286; National Key Research and Development Program, No. 2018YFC1704202 and No. 2020YFE0201800; University Scientific Research Projects of Anhui, No. KJ2020A0401 and No. KJ2019A0442; and Province Science Foundation of Anhui, No. 1708085QH213.
Institutional review board statement: The Institutional Review Board approval is not applicable in this study because it did not involve human beings.
Institutional animal care and use committee statement: All animal experiments were performed in accordance with the guidelines approved by the Animal Ethics Committee of Diabetes Institute, Anhui Academy Chinese Medicine (approval No. 2017AH-06).
Conflict-of-interest statement: None of the authors have any conflicts of interest to declare.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Zhao-Hui Fang, PhD, Chief Doctor, Department of Endocrinology, The First Affiliated Hospital of Anhui University of Chinese Medicine, No. 117 Meishan Road, Hefei 230031, Anhui Province, China.
Received: October 24, 2020
Peer-review started: October 24, 2020
First decision: November 23, 2020
Revised: December 17, 2020
Accepted: January 13, 2021
Article in press: January 13, 2021
Published online: February 28, 2021

A recent investigation showed that the prevalence of type 2 diabetes mellitus (T2DM) is 12.8% among individuals of Han ethnicity. Gut microbiota has been reported to play a central role in T2DM. Goto-Kakizaki (GK) rats show differences in gut microbiota compared to non-diabetic rats. Previous studies have indicated that berberine could be successfully used to manage T2DM. We sought to understand its hypoglycaemic effect and role in the regulation of the gut microbiota.


To determine whether berberine can regulate glucose metabolism in GK rats via the gut microbiota.


GK rats were acclimatized for 1 wk. The GK rats were randomly divided into three groups and administered saline (Mo), metformin (Me), or berberine (Be). The observation time was 8 wk, and weight, fasting blood glucose (FBG), insulin, and glucagon-like peptide-1 (GLP-1) were measured. Pancreatic tissue was observed for pathological changes. Additionally, we sequenced the 16S rRNA V3-V4 region of the gut microbiota and analysed the structure.


Compared with the Mo group, the Me and Be groups displayed significant differences in FBG (P < 0.01) and GLP-1 (P < 0.05). A significant decrease in weight and homeostatic model assessment-insulin resistance was noted in the Be group compared with those in the Me group (P < 0.01). The pancreatic islets of the Me- and Be-treated rats showed improvement in number, shape, and necrosis compared with those of Mo-treated rats. A total of 580 operational taxonomic units were obtained in the three groups. Compared to the Mo group, the Me and Be groups showed a shift in the structure of the gut microbiota. Correlation analysis indicated that FBG was strongly positively correlated with Clostridia_UCG-014 (P < 0.01) and negatively correlated with Allobaculum (P < 0.01). Body weight showed a positive correlation with Desulfovibrionaceae (P < 0.01) and a negative correlation with Akkermansia (P < 0.01). Importantly, our results demonstrated that Me and Be could significantly decrease Bacteroidetes (P < 0.01) and the Bacteroidetes/Firmicutes ratio (P < 0.01). Furthermore, Muribaculaceae (P < 0.01; P < 0.05) was significantly decreased in the Me and Be groups, and Allobaculum (P < 0.01) was significantly increased.


Berberine has a substantial effect in improving metabolic parameters and modulating the gut microbiota composition in T2DM rats.

Keywords: Type 2 diabetes mellitus, Amelioration of hyperglycaemia, Modulation of gut microbiota, Berberine, Metformin, Goto-Kakizaki rats

Core Tip: Recent studies suggested that the gut microbiota has an essential role in type 2 diabetes mellitus. Our study verifies the effects of berberine in regulating glucose metabolism and reducing pancreas injury in Goto-Kakizaki rats. Berberine also provides an alternative means of modulating the gut microbiota. The results revealed evidence of a decrease in Desulfobacterota, Desulfovibrionaceae, and Clostridia_UCG-014 and an increase in Verrucomicrobiota, Akkermansia, and Allobaculum. Correlation analysis indicated that fasting blood glucose was strongly positively correlated with Clostridia_UCG-014 and negatively correlated with Allobaculum.