Role of duodenal mucosal resurfacing in controlling diabetes in rats.

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.