A specific gut microbiota signature is associated with an enhanced GLP-1 and GLP-2 secretion and improved metabolic control in patients with type 2 diabetes after metabolic Roux-en-Y gastric bypass

Front Endocrinol (Lausanne). 2023 Oct 17:14:1181744. doi: 10.3389/fendo.2023.1181744. eCollection 2023.

Abstract

Objective: To determine changes in incretins, systemic inflammation, intestinal permeability and microbiome modifications 12 months after metabolic RYGB (mRYGB) in patients with type 2 diabetes (T2D) and their relationship with metabolic improvement.

Materials and methods: Prospective single-center non-randomized controlled study, including patients with class II-III obesity and T2D undergoing mRYGB. At baseline and one year after surgery we performed body composition measurements, biochemical analysis, a meal tolerance test (MTT) and lipid test (LT) with determination of the area under the curve (AUC) for insulin, C-peptide, GLP-1, GLP-2, and fasting determinations of succinate, zonulin, IL-6 and study of gut microbiota.

Results: Thirteen patients aged 52.6 ± 6.5 years, BMI 39.3 ± 1.4 kg/m2, HbA1c 7.62 ± 1.5% were evaluated. After mRYGB, zonulin decreased and an increase in AUC after MTT was observed for GLP-1 (pre 9371 ± 5973 vs post 15788 ± 8021 pM, P<0.05), GLP-2 (pre 732 ± 182 vs post 1190 ± 447 ng/ml, P<0.001) and C- peptide, as well as after LT. Species belonging to Streptococaceae, Akkermansiacea, Rickenellaceae, Sutterellaceae, Enterobacteriaceae, Oscillospiraceae, Veillonellaceae, Enterobacterales_uc, and Fusobacteriaceae families increased after intervention and correlated positively with AUC of GLP-1 and GLP-2, and negatively with glucose, HbA1c, triglycerides and adiposity markers. Clostridium perfringens and Roseburia sp. 40_7 behaved similarly. In contrast, some species belonging to Lachnospiraceae, Erysipelotricaceae, and Rumnicocaceae families decreased and showed opposite correlations. Higher initial C-peptide was the only predictor for T2D remission, which was achieved in 69% of patients.

Conclusions: Patients with obesity and T2D submitted to mRYGB show an enhanced incretin response, a reduced gut permeability and a metabolic improvement, associated with a specific microbiota signature.

Keywords: bariatric surgery; incretin; microbiota; severe obesity; type 2 diabetes remission.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • C-Peptide / metabolism
  • Diabetes Mellitus, Type 2* / complications
  • Gastric Bypass*
  • Gastrointestinal Microbiome*
  • Glucagon-Like Peptide 1 / metabolism
  • Glucagon-Like Peptide 2
  • Humans
  • Incretins / metabolism
  • Obesity / metabolism
  • Prospective Studies

Substances

  • Glucagon-Like Peptide 1
  • C-Peptide
  • Incretins
  • Glucagon-Like Peptide 2

Grants and funding

NVil is the recipient of grants “PI11/01960; PI14/01997; PI17/01556 and PI22/01773” funded by Instituto de Salud Carlos III and co-funded by European Union ERDF, “A way to build Europe”. LH-M obtained the research grant 20PSJ027 from Societat Catalana d’Endocrinologia i Nutrició SCEN. JV has funding from Instituto de Salud Carlos III through the PI17/01503 and PI 20/000475 co-funded by European Union ERDF, “A way to build Europe”. SF-V has funding from the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund ERDF SAF2015-65019-R. The Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders CIBERDEM CB07708/0012 is an initiative of the Instituto de Salud Carlos III. SF-V acknowledges support from the Miguel Servet tenure-track program CP10/00438 and CPII16/0008 from the Fondo de Investigacioín Sanitaria FIS co-financed by the ERDF.