Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Mar 15, 2025; 16(3): 102277
Published online Mar 15, 2025. doi: 10.4239/wjd.v16.i3.102277
Role of duodenal mucosal resurfacing in controlling diabetes in rats
Li-Juan Nie, Zhe Cheng, Yi-Xian He, Qian-Hua Yan, Yao-Huan Sun, Xin-Yi Yang, Jie Tian, Peng-Fei Zhu, Jiang-Yi Yu, Hui-Ping Zhou, Xi-Qiao Zhou
Li-Juan Nie, Zhe Cheng, Yi-Xian He, Qian-Hua Yan, Yao-Huan Sun, Xin-Yi Yang, Jie Tian, Peng-Fei Zhu, Jiang-Yi Yu, Xi-Qiao Zhou, Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
Li-Juan Nie, School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
Hui-Ping Zhou, Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23284, United States
Co-first authors: Li-Juan Nie and Zhe Cheng.
Author contributions: Zhou XQ and Nie LJ conceived the idea and designed the study; Nie LJ, Cheng Z, He YX and Zhou XQ wrote the study protocol; Yan QH, Sun YH, Yang XY, Zhu PF, Tian J, Yu JY, and Zhou HP participated in the discussion and modification of the experimental plan; Nie LJ, Cheng Z and He YX performed the research and data analyses; Nie LJ wrote the manuscript; Zhou HP and Zhou XQ revised the manuscript; All authors had approved the final manuscript for submission.
Supported by the National Natural Science Foundation of China, No. 82474318; the Jiangsu Administration of Traditional Chinese Medicine, No. zt202105; Subject of Jiangsu Province Hospital of Chinese Medicine, No. Y2021rc22; and a Research Career Scientist Award (to Zhou HP) from the Department of Veterans Affairs (United States), No. 2IK6BX004477-06.
Institutional review board statement: The study does not involve any human experiments.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Jiangsu Center for Safety Evaluation of Drugs (No. IACUC-20220613-01).
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: Detailed methods and datasets supporting the findings of the present study are available from the corresponding author upon request.
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: Xi-Qiao Zhou, PhD, Professor, Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, No. 155 Hanzhong Road, Nanjing 210029, Jiangsu Province, China. zhouxiqiao@njucm.edu.cn
Received: October 15, 2024
Revised: December 9, 2024
Accepted: January 3, 2025
Published online: March 15, 2025
Processing time: 98 Days and 3.2 Hours
Abstract
BACKGROUND

The duodenum plays a significant role in metabolic regulation, and thickened mucous membranes are associated with insulin resistance. Duodenal mucosal resurfacing (DMR), a new-style endoscopic procedure using hydrothermal energy to ablate this thickened layer, shows promise for enhancing glucose and lipid metabolism in type 2 diabetes (T2D) patients. However, the mechanisms driving these improvements remain largely unexplored.

AIM

To investigate the mechanisms by which DMR improves metabolic disorders using a rat model.

METHODS

Rats with T2D underwent a revised DMR procedure via a gastric incision using a specialized catheter to abrade the duodenal mucosa. The duodenum was evaluated using histology, immunofluorescence, and western blotting. Serum assays measured glucose, lipid profiles, lipopolysaccharide, and intestinal hormones, while the gut microbiota and metabolomics profiles were analyzed through 16S rRNA gene sequencing and ultra performance liquid chromatography-mass spectrum/mass spectrum, severally.

RESULTS

DMR significantly improved glucose and lipid metabolic disorders in T2D rats. It increased the serum levels of cholecystokinin, gastric inhibitory peptide, and glucagon-like peptide 1, and reduced the length and depth of duodenal villi and crypts. DMR also enhanced the intestinal barrier integrity and reduced lipopolysaccharide translocation. Additionally, DMR modified the gut microbiome and metabolome, particularly affecting the Blautia genus. Correlation analysis revealed significant links between the gut microbiota, metabolites, and T2D phenotypes.

CONCLUSION

This study illustrates that DMR addresses metabolic dysfunctions in T2D through multifaceted mechanisms, highlighting the potential role of the Blautia genus on T2D pathogenesis and DMR’s therapeutic impact.

Keywords: Type 2 diabetes; Duodenal mucosal resurfacing; Gut microbiota; Insulin resistance; Blautia; Gastric inhibitory peptide; Glucagon-like peptide 1

Core Tip: Duodenum is a particular metabolic signaling center, and the thickened mucous membranes cause duodenal dysfunction and promote insulin resistance. This study explored the mechanisms by which duodenal mucosal resurfacing (DMR) affects type 2 diabetes (T2D) using a rat model. It highlights the potential role of the Blautia genus in the pathogenesis of T2D and the therapeutic effect of DMR. The results provide a theoretical basis for performing DMR in humans with T2D and identify several areas requiring further research.