1784-P: Duodenal Mucosal Resurfacing Ameliorates Type 2 Diabetes by Reshaping Gut Microbiota and Attenuating Microbial-Driven Inflammation and Bile Acid Dysmetabolism in Rats

Introduction and Objective: Duodenal mucosal resurfacing (DMR) shows promise in treating T2D, but its mechanism related to the duodenal microbiome remains unclear. We investigated whether DMR exerts therapeutic effects by modulating the duodenal microbiota and its related metabolic functions. Methods: T2D was induced in male SD rats by high-fat diet and streptozotocin. Rats were divided into normal control (NC_sham), T2D with sham surgery (T2D_sham), and T2D with DMR surgery (T2D_DMR) groups. Duodenal content was analyzed using 16S rRNA gene sequencing, metagenomics, and targeted metabolomics. Metabolic parameters and duodenal morphology were assessed. Results: DMR significantly improved glycemic control and glucose tolerance, and reduced serum triglycerides. It reversed T2D-associated duodenal villus elongation. Microbiota analysis revealed that DMR corrected the dysbiosis in T2D_sham rats, characterized by reduced Lactobacillus and enriched opportunistic pathogens (e.g., Corynebacterium, Aerococcus). Metagenomics identified significant upregulation of pro-inflammatory pathways (e.g., bacterial arabinogalactan/lipoarabinomannan biosynthesis, tuberculosis pathway) and metabolic pathways (e.g., inositol phosphate metabolism) in the T2D_sham group. Metabolomics showed elevated levels of specific bile acids (e.g., GDCA, GHDCA) and decreased beneficial metabolites (TUDCA, palmitoleic acid) in T2D_sham rats. Crucially, correlation networks linked Corynebacterium species to these pro-inflammatory pathways, altered bile acids, and higher blood glucose. Conclusion: DMR alleviates T2D by remodeling the duodenal microbiota, suppressing opportunistic pathogen-driven pro-inflammatory functional pathways, and restoring a healthier bile acid metabolic profile. This study elucidates a microbiota-dependent mechanism for DMR's metabolic benefits. Disclosure X. Zhou: None. Y. Cao: None.