Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 21, 2023; 29(39): 5471-5482
Published online Oct 21, 2023. doi: 10.3748/wjg.v29.i39.5471
Enhanced glucose homeostasis via Clostridium symbiosum-mediated glucagon-like peptide 1 inhibition of hepatic gluconeogenesis in mid-intestinal bypass surgery
Xin Luo, Fang Tao, Cai Tan, Chi-Ying Xu, Zhi-Hua Zheng, Qiang Pang, Xiang-An He, Jia-Qing Cao, Jin-Yuan Duan
Xin Luo, Fang Tao, Chi-Ying Xu, Jin-Yuan Duan, Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330000, Jiangxi Province, China
Cai Tan, Department of Women’s Health, Jiangxi Maternal and Child Health Hospital, Nanchang 330000, Jiangxi Province, China
Zhi-Hua Zheng, Qiang Pang, Xiang-An He, Jia-Qing Cao, Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330000, Jiangxi Province, China
Author contributions: Luo X, Tan C, Cao JQ, and Duan JY contributed to the conception of the study; Luo X, Tan C, Zheng ZH, and Pang Q performed the experiment; Luo X, Tan C, and Duan JY contributed significantly to analysis and manuscript preparation; Luo X, Tao F, Xu CY, Zheng ZH, Pang Q, He XA, Cao JQ, and Duan JY helped perform the analysis with constructive discussions; Luo X, Tan C, and Duan JY performed the data analyses and wrote the manuscript.
Supported by National Natural Science Foundation of China, No. 82060161, 81960154, and 81760156; Jiangxi Provincial Youth Science Foundation, No. 2018ACB21040; Natural Science Foundation of Jiangxi Province, No. 20212BAB206020; and Foundation of Health commission of Jiangxi Province, No. SKJP220225830.
Institutional animal care and use committee statement: The study was reviewed and approved by the the Animal Ethics Committee of Nanchang University.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at duanjy2022@outlook.com.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jin-Yuan Duan, PhD, Associate Chief Physician, Department of General Surgery, The First Affiliated Hospital of Nanchang University, No. 1519 Dongyue Avenue, Nanchang 330000, Jiangxi Province, China. duanjy2022@outlook.com
Received: July 14, 2023
Peer-review started: July 14, 2023
First decision: September 6, 2023
Revised: September 11, 2023
Accepted: October 11, 2023
Article in press: October 11, 2023
Published online: October 21, 2023
ARTICLE HIGHLIGHTS
Research background

The exact mechanism by which mid-small intestinal bypass (MSIB) improves glucose metabolism in diabetic rats is not fully understood.

Research motivation

To explore the role of the mid-small intestine in the onset and progression of diabetes.

Research objectives

The aim of this study was to elucidate the mechanisms by which MSIB improves glucose metabolism.

Research methods

Streptozotocin was used to induce diabetes mellitus in Sprague-Dawley rats at a dose of 60 mg/kg. The rats were then randomly divided into two groups: The MSIB group and the sham group (underwent switch laparotomy). Following a 6-wk recovery period post-surgery, the rats underwent various assessments, including metabolic parameter testing, analysis of liver glycogen levels, measurement of key gluconeogenic enzyme activity, characterization of the gut microbiota composition, evaluation of hormone levels, determination of bile acid concentrations, and assessment of the expression of the intestinal receptors Takeda G protein-coupled receptor 5 and farnesoid X receptor.

Research results

The MSIB group of rats exhibited improved glucose and lipid metabolism, increased hepatic glycogen content, and decreased expression of key gluconeogenic enzymes (phosphoenolpyruvate carboxykinase 1 and glucose-6-phosphatase). Notably, this group showed a substantial rise in specific intestinal bacteria, including Lactobacillus, Clostridium symbiosum, Ruminococcus gnavus, and Bilophila. Additionally, elevated levels of secondary bile acids, such as lithocholic acid, were observed. Importantly, changes in the gut microbiota were significantly correlated with the expression of gluconeogenic enzymes and glucagon-like peptide 1 (GLP-1) at 6 wk post-surgery, suggesting their potential involvement in regulating glucose. These findings underscore the beneficial impact of mid-small intestine bypass on glucose metabolism and its modulation of the gut microbiota.

Research conclusions

This study shows that postoperative introduction of intestinal Clostridium symbiosum in the mid-small intestine improves glucose metabolism in non-obese diabetic rats. This enhancement is linked to increased inhibition of hepatic gluconeogenesis mediated by GLP-1, leading to a positive impact on glucose regulation.

Research perspectives

This study explores partial mechanisms of the interaction between gut microbiota and host metabolism, providing a theoretical foundation for non-surgical interventions in diabetes-related metabolic disorders.