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: http://creativecommons.org/Licenses/by-nc/4.0/
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. fangzhaohui1111@163.com
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
Processing time: 124 Days and 18.7 Hours
ARTICLE HIGHLIGHTS
Research background

Type 2 diabetes mellitus (T2DM) has become a critical and urgent human health concern worldwide. Accumulating evidence has suggested that diabetes is also associated with gut microbiota composition and homeostasis. Hence, regulators of gut microbiota may become potential alternative targets for diabetes treatment. For many years, studies have shown that traditional Chinese medicine (TCM) exhibits an effect against the development of T2DM and can be used to treat T2DM. Thus, exploring a TCM monomer that can effectively regulate gut microbiota could benefit the prognosis of T2DM.

Research motivation

Goto-Kakizaki (GK) rats have been widely used to study T2DM, and berberine has been used for T2DM. At present, there are many reports indicating that berberine can regulate blood glucose, improve blood lipids, and reduce insulin resistance. Some studies have reported that berberine repairs the gut barrier structure and alters the diversity of the gut microbiota. Therefore, this study aimed to verify the effect of berberine treatment in GK rats and explore the underlying mechanism about gut microbiota.

Research objectives

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

Research methods

Male GK rats were randomly divided into a saline (Mo), metformin (Me), or berberine (Be) group, with ten rats in each group. The observation time was 8 wk, and weight, fasting blood glucose (FBG), insulin, and glucagon-like peptide-1 (GLP-1) were measured. The pathology of the pancreatic tissue was observed. We also sequenced the 16S rRNA V3-V4 region of the gut microbiota and analysed the relationship to metabolic parameters.

Research results

The FBG, GLP-1, and homeostatic model assessment-insulin resistance (HOMA-IR) levels and pancreatic islets in the Me and Be groups were significantly different from those of the Mo group. Correlation analysis indicated that FBG was strongly positively correlated with Clostridia_UCG-014 and negatively correlated with Allobaculum. Importantly, our results demonstrated that Me and Mo could significantly decrease Bacteroidetes and the Bacteroidetes/Firmicutes ratio. 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.

Research conclusions

Berberine has a substantial effect in regulating the gut microbiota to improve metabolic parameters in GK rats.

Research perspectives

We observed that berberine might decrease FBG, reduce HOMA-IR, and increase GLP-1 in GK rats. Further investigation of the underlying molecular mechanisms of berberine in regulating the gut farnesoid X receptor and/or the G-protein-coupled receptor is required to provide experimental evidence for wider clinical and experimental usage.