You are here

  • Home
  • Archive
  • Volume 58, Issue 8
  • Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability

Article Text

Article menu
XML
Inflammatory bowel disease
1506
Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability
  1. P D Cani1,
  2. S Possemiers2,
  3. T Van de Wiele2,
  4. Y Guiot3,
  5. A Everard1,
  6. O Rottier1,
  7. L Geurts1,
  8. D Naslain1,4,
  9. A Neyrinck1,
  10. D M Lambert4,
  11. G G Muccioli5,
  12. N M Delzenne1
  1. 1
    Unit of Pharmacokinetics, Metabolism, Nutrition and Toxicology, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium
  2. 2
    Laboratory of Microbial Ecology and Technology, Faculty of Bioscience Engineering, Ghent University, Gent, Belgium
  3. 3
    Department of Pathology, Université catholique de Louvain, Brussels, Belgium
  4. 4
    Medicinal Chemistry and Radiopharmacy Unit, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium
  5. 5
    Laboratory of Chemical and Physico-chemical Analysis of Drugs (CHAM), Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium
  1. Dr P D Cani, UCL, Unit PMNT-7369, Av E Mounier, 73/69, B-1200 Brussels, Belgium; patrice.cani{at}uclouvain.be; or Professor NM Delzenne, UCL, Unit PMNT-7369, Av R Mounier, 73/69, B-1200 Brussels, Belgium; nathalie.delzenne{at}uclouvain.be

Abstract

Background and aims: Obese and diabetic mice display enhanced intestinal permeability and metabolic endotoxaemia that participate in the occurrence of metabolic disorders. Our recent data support the idea that a selective increase of Bifidobacterium spp. reduces the impact of high-fat diet-induced metabolic endotoxaemia and inflammatory disorders. Here, we hypothesised that prebiotic modulation of gut microbiota lowers intestinal permeability, by a mechanism involving glucagon-like peptide-2 (GLP-2) thereby improving inflammation and metabolic disorders during obesity and diabetes.

Methods: Study 1: ob/ob mice (Ob-CT) were treated with either prebiotic (Ob-Pre) or non-prebiotic carbohydrates as control (Ob-Cell). Study 2: Ob-CT and Ob-Pre mice were treated with GLP-2 antagonist or saline. Study 3: Ob-CT mice were treated with a GLP-2 agonist or saline. We assessed changes in the gut microbiota, intestinal permeability, gut peptides, intestinal epithelial tight-junction proteins ZO-1 and occludin (qPCR and immunohistochemistry), hepatic and systemic inflammation.

Results: Prebiotic-treated mice exhibited a lower plasma lipopolysaccharide (LPS) and cytokines, and a decreased hepatic expression of inflammatory and oxidative stress markers. This decreased inflammatory tone was associated with a lower intestinal permeability and improved tight-junction integrity compared to controls. Prebiotic increased the endogenous intestinotrophic proglucagon-derived peptide (GLP-2) production whereas the GLP-2 antagonist abolished most of the prebiotic effects. Finally, pharmacological GLP-2 treatment decreased gut permeability, systemic and hepatic inflammatory phenotype associated with obesity to a similar extent as that observed following prebiotic-induced changes in gut microbiota.

Conclusion: We found that a selective gut microbiota change controls and increases endogenous GLP-2 production, and consequently improves gut barrier functions by a GLP-2-dependent mechanism, contributing to the improvement of gut barrier functions during obesity and diabetes.

http://dx.doi.org/10.1136/gut.2008.165886

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Supplementary materials

    Footnotes

    • Competing interests: None.

    • Funding: PDC is Postdoctoral Researcher from the FRS-FNRS (Fonds de la Recherche Scientifique) Belgium. NMD and PDC are recipients of FSR and FRSM subsidies (Fonds speciaux de recherches, UCL, Belgium; Fonds de la recherché scientifique medicale, Belgium). SP and TVDW are Postdoctoral Researchers from the Research Foundation – Flanders (Fonds voor Wetenschappelijk Onderzoek (FWO) – Vlaanderen).

    • See Commentary, p 1044

    • Ethics approval: Animal experiments were approved by the local ethics committee and housing conditions were as specified by the Belgian Law of 14 November 1993 on the protection of laboratory animals (agreement n° LA 1230314).

    Linked Articles