Insulin resistance modulates gut microbiota and incretin response remodeling after bariatric surgery in severe obesity
Puig, Rocío (Institut de Recerca Sant Pau)
Rodríguez-Peña, M-Mar (Hospital Universitari Joan XXIII de Tarragona. Institut d'Investigació Sanitària Pere Virgili)
Hernández-Montoliu, Laura (Institut d'Investigació Biomèdica de Bellvitge)
Astiarraga, Brenno (Hospital Universitari Joan XXIII de Tarragona. Institut d'Investigació Sanitària Pere Virgili)
Martínez, Eva (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Balibrea Del Castillo, José María (Universitat Autònoma de Barcelona. Departament de Cirurgia)
Llauradó, Gemma (Institut Hospital del Mar d'Investigacions Mèdiques)
Tarascó, Jordi (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Caballero, Albert (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Joaquín, Clara (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Puig Domingo, Manuel (Universitat Autònoma de Barcelona. Departament de Medicina)
Vilarrasa, Nuria (Institut d'Investigació Biomèdica de Bellvitge)
Fernández-Veledo, Sonia (Hospital Universitari Joan XXIII de Tarragona. Institut d'Investigació Sanitària Pere Virgili)
Vendrell, Joan (Hospital Universitari Joan XXIII de Tarragona. Institut d'Investigació Sanitària Pere Virgili)
Pellitero, Silvia (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)

Date:	2025
Abstract:	This study aims to assess the impact of insulin resistance (IR) on gut microbiota (GM) composition, incretin responses, and metabolic outcomes following sleeve gastrectomy (SG) in people with severe obesity who do not have diabetes. Methods: A prospective single-center study encompassed patients with severe obesity and normal glucose tolerance who underwent SG. Participants were stratified into two cohorts based on the magnitude of their insulin resistance state, as determined by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index: high-IR (Hi-IR; HOMA-IR 95th percentile) and low-IR (Lo-IR; HOMA-IR < 25th percentile). Body composition measurements, biochemical analyses, and microbiota assessments were performed before and six months post-surgery. Additionally, the responses to a standardized meal tolerance test (MTT) of glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) were evaluated. Results: The study cohort consisted of 18 patients (9 with Hi-IR and 9 with Lo-IR), with a mean age of 48. 8 ± 9. 2 years and a mean body mass index (BMI) of 45. 03 ± 4. 82 kg/m². Six months post-surgery, the mean percentage of total weight loss (WL) was 26. 5 ± 6%, with both groups exhibiting enhanced secretion of GLP-1 and GLP-2 following MTT. At baseline, participants exhibited distinct microbiota profiles; the Hi-IR group showed a higher relative abundance of Prevotella species, which are previously associated with adverse metabolic and inflammatory profiles. Post-surgery, both groups exhibited positive incretin responses and significant modifications in GM composition. Notably Hi-IR people experienced more 146 pronounced changes in microbial diversity, including increases in Akkermansia and Veillonella species and decreases in Prevotella species. Enhanced GLP-1 and GLP-2 responses were correlated with WL and metabòlic improvement, particularly in the Lo-IR population. Conclusions: These findings underscore the role of GM in metabolic changes and surgical outcomes after SG. Targeting gut microbiota may offer a promising avenue for improving obesity treatment strategies.
Grants:	Ministerio de Economía y Competitividad PI14/00228 Instituto de Salud Carlos III PI17/01503 Instituto de Salud Carlos III PI20/00338 Instituto de Salud Carlos III PI23/01133 Ministerio de Economía y Competitividad PI14/00633 Instituto de Salud Carlos III PI17/00915 Instituto de Salud Carlos III PI20/00114 Instituto de Salud Carlos III PI23/01289 Ministerio de Economía y Competitividad PI14/01997 Instituto de Salud Carlos III PI17/01556 Instituto de Salud Carlos III PI22/01773 Ministerio de Ciencia e Innovación RTI2018-093919-B-100 Ministerio de Ciencia e Innovación PID2021-122480OB-584-100 "la Caixa" Foundation 100010434 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-01409 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00089
Rights:	Aquest material està protegit per drets d'autor i/o drets afins. Podeu utilitzar aquest material en funció del que permet la legislació de drets d'autor i drets afins d'aplicació al vostre cas. Per a d'altres usos heu d'obtenir permís del(s) titular(s) de drets.
Language:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Subject:	Insulin resistance ; Incretin ; Microbiota ; Severe obesity ; Bariatric surgery
Published in:	International journal of obesity, 2026 , ISSN 1476-5497

DOI: 10.1038/s41366-025-01971-7

Postsprint

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles