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Exploring the Role of Duodenal Resurfacing in Diabetes Improvement
43 Pages Posted: 21 Feb 2024
More...Abstract
Background: The duodenum has emerged as a key player in metabolic regulation, where its thickened mucosa is linked to insulin resistance. Duodenal mucosal resurfacing (DMR), a novel 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.
Methods: In this study, T2D rats underwent a revised DMR procedure via a gastric incision and a specialized catheter, which abraded the duodenal mucosa. We evaluated the duodenum using histology, immunofluorescence, and Western blotting. Serum assays measured glucose, lipid profiles, lipopolysaccharide (LPS), and intestinal hormones, while the gut microbiota and metabolomics profiles were analyzed through 16S rRNA gene sequencing and UPLC-MS/MS, respectively.
Findings: DMR significantly improved glucose and lipid metabolic disorders in T2D rats. It increased serum levels of cholecystokinin, GIP and GLP-1, while reducing the length and depth of duodenal villi and crypt. The procedure also enhanced intestinal barrier integrity, minimizing LPS translocation. Additionally, DMR modified the gut microbiome and metabolome, particularly affecting the Blautia genus. Correlation analysis underscored significant links between the gut microbiota, metabolites, and T2D phenotypes.
Interpretation: This study illustrates that DMR addresses metabolic dysfunctions in T2D through multifaceted mechanisms, highlighting the potential role of the Blautia genus T2D pathogenesis and DMR’s therapeutic impact.
Funding: This study was supported by the Project Funded by the Priority Academic Program
Development of Jiangsu Higher Education Institutions (PAPD, 035062005002-14),
the special research project of Jiangsu Administration of traditional Chinese medicine
(zt202105), and the Project Funded by Jiangsu Province Hospital of Chinese
Medicine (kkzx01). Dr. Zhou is the recipient of a Research Career Scientist Award
from the Department of Veterans Affairs (IK6BX004477), USA.
Declaration of Interest: The all authors declare that there is no conflict of interests
regarding the publication of this article.
Ethical Approval: The animal procedures were performed according to the Principles of Laboratory Animal Care and approved by the Ethics Committee of Jiangsu Center for Safety Evaluation of Drugs.
Keywords: type 2 diabetes (T2D), Duodenal mucosal resurfacing (DMR), gut microbiota, Insulin resistance, GIP, GLP-1
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