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
Abstract
BACKGROUND

The small intestine is known to play a crucial role in the development and remission of diabetes mellitus (DM). However, the exact mechanism by which mid-small intestinal bypass improves glucose metabolism in diabetic rats is not fully understood.

AIM

To elucidate the mechanisms by which mid-small intestinal bypass improves glucose metabolism.

METHODS

Streptozotocin (STZ) was used to induce DM in Sprague-Dawley (SD) rats at a dose of 60 mg/kg. The rats were then randomly divided into two groups: The mid-small intestine bypass (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.

RESULTS

The MSIB group of rats demonstrated improved glucose metabolism and lipid metabolism, along with increased hepatic glycogen content. Furthermore, there was a decrease in the expression of the key gluconeogenic enzymes phosphoenolpyruvate carboxykinase 1 and glucose-6-phosphatase. Importantly, the MSIB group exhibited a substantial increase in the abundances of intestinal Lactobacillus, Clostridium symbiosum, Ruminococcus gnavus, and Bilophila. Moreover, higher levels of secondary bile acids, such as intestinal lithocholic acid, were observed in this group. Remarkably, the changes in the gut microbiota showed a significant correlation with the expression of key gluconeogenic enzymes and glucagon-like peptide 1 (GLP-1) at 6 wk postoperatively, highlighting their potential role in glucose regulation. These findings highlight the beneficial effects of mid-small intestine bypass on glucose metabolism and the associated modulation of the gut microbiota.

CONCLUSION

The findings of this study demonstrate that the introduction of postoperative intestinal Clostridium symbiosum in the mid-small intestine contributes to the enhancement of glucose metabolism in nonobese diabetic rats. This improvement is attributed to the increased inhibition of hepatic gluconeogenesis mediated by GLP-1, resulting in a favorable modulation of glucose homeostasis.

Keywords: Gut micobiome, Glucagon-like peptide-1, Glucose metablism, Bile acid, Bariatric surgery, Gluconeogenesis

Core Tip: Intestinal function plays a pivotal role in the onset, progression, and alleviation of diabetes. However, research on surgical procedures and functions involving the mid-small intestine is limited. The precise mechanisms by which the mid-small intestine improves glucose metabolism in diabetic rats remain largely unclear. This study explores the effects of mid-small intestine bypass surgery on diabetic rats. Post-surgery, there was an increase in the abundance of Clostridium symbiosum in the rat gut, which contributed to improved glucose metabolism through the inhibition of hepatic gluconeogenesis mediated by glucagon-like peptide 1. These findings provide a theoretical basis for non-surgical interventions in the treatment of metabolic disorders associated with diabetes.