ENDOBARRIER®, A DUODENAL-JEJUNAL BYPASS LINER DEVICE, ALTERS THE GLOBAL METABOLIC AND THE GUT BACTERIAL PROFILES OF PATIENTS WITH OBESITY AND DIABETES
Aruchuna Ruban1, Ghadah Aldubaikhi1, Nicholas A. Johnson1, Michael A. Glaysher2, Navpreet Chhina1, James Byrne2, Julian Marchesi1, Julian P. Teare1, Anthony P. Goldstone1, Alexander Miras1, Jia V. Li*1
1Imperial College London, London, United Kingdom; 2University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
Background: Roux-en-Y gastric bypass (RYGB) surgery has proven highly effective in improving type 2 diabetes mellitus (T2DM). One of the possible mechanisms is through the exclusion of the foregut from the food digestion and absorption. A duodenal-jejunal bypass liner device or EndoBarrier®, mimicking such exclusion in RYGB, offers a less invasive option compared to the surgery. EndoBarrier has been shown to reduce body weight and improve glycemic control; however, the metabolic and the gut microbial changes have not been explored in a randomized controlled clinical trial. We aimed to investigate EndoBarrier-induced perturbations in both fecal bacterial and global metabolic profiles of urine, serum and feces.
Methods: Participants with obesity and uncontrolled T2DM on oral glucose-lowering medication were recruited into this multicenter, randomized, controlled, and open-label trial (ClinicalTrials.gov Identifier NCT02459561) carried out at Imperial College London and University Hospital Southampton NHS Foundation Trusts. Biofluid samples were collected from a control group receiving conventional T2DM therapy with lifestyle modification, and EndoBarrier group during a 12-month treatment period and a 1-year follow-up after the removal of the device. All samples were analyzed using proton nuclear magnetic resonance (1H NMR) spectroscopy-based metabolic phenotyping approach and 16S rRNA gene sequencing was used to obtain bacterial profiles.
Results and Discussion: Both EndoBarrier and control groups showed significant reductions in body mass index, HOMA-IR scores, fasting blood glucose and HbA1c levels during the treatment period (within 12 months into the treatment) compared to the baseline. Consistent with previously reported findings from RYGB surgery, EndoBarrier resulted in increased relative abundance of fecal Gammaproteobacteria (e.g., Klebsiella, Escherichia_Shigella) and Bacilli and reduced relative abundance of Clostridia. Significant differences from baseline in metabolic profiles of urine and faeces were observed 6 and 12 months into the treatment. These included higher urinary concentrations of phenylacetylglutamine, indoxyl sulfate, and 4-cresyl sulfate and fecal concentrations of tyramine and lactate, indicating enhanced host-microbial co-metabolism induced by EndoBarrier but not the conventional T2DM therapy. These changes reverted towards baseline levels 1 year after device explantation.
Conclusion: This is the first study to explore the metabolic profiles of patients receiving the EndoBarrier treatment. These metabolic changes highlighted shifts in the gut bacterial functions towards amino acid metabolism. Their association with the clinical outcomes warrants further studies.
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