A Changed Gut Microbiota Diversity Is Associated With Metabolic Improvements After Duodenal Mucosal Resurfacing With Glucagon-Like-Peptide-1 Receptor Agonist in Type 2 Diabetes in a Pilot Study

INTRODUCTION: The gut microbiota influences and interacts with the host metabolism through effects on nutrient metabolism and digestion. Duodenal Mucosal Resurfacing (DMR) is a novel endoscopic procedure involving duodenal mucosal ablation by the use of hydrothermal energy. DMR, when combined with a glucagon-like peptide-1 receptor agonist (GLP-1RA), resulted in discontinuation of exogenous insulin treatment in 69% of patients with insulin dependent type 2 diabetes mellitus (T2DM) in the INSPIRE study. These patients also experienced improved glycaemic control and metabolic health. We thus investigated if these clinical effects were associated with a change in gut microbiota alpha and beta diversity. METHODS: Faecal samples from the 16 patients were obtained for Illumina shotgun sequencing at baseline and 3 months after DMR. We assessed alpha and beta diversity of the gut microbiota in these samples and analysed its correlations with changes in HbA1c, body weight, and liver MRI proton density fat fraction (PDFF). RESULTS: HbA1c correlated negatively with alpha diversity (p=0.011, rho: -0.62) whereas changes in PDFF correlated significantly with beta diversity (p=0.036, rho: 0.55) 3 months after initiation of the combined intervention. These correlations with metabolic parameters were observed despite finding no change in gut microbiota diversity at 3 months post DMR. DISCUSSION: The correlation between gut microbiota richness (alpha diversity) and HbA1c as well as the change in PDFF and changed microbiota composition (beta diversity) suggests that changed gut microbiota diversity is associated with metabolic improvements after DMR in combination with glucagon-like-peptide-1 receptor agonist in type 2 diabetes. Larger controlled studies are however needed to find causal links between DMR with GLP-1RA, the gut microbiota, and improvements in metabolic health.