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Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability
  1. Patrice D Cani (patrice.cani{at}uclouvain.be)
  1. Université catholique de Louvain, Belgium
    1. Sam Possemiers
    1. Ghent University, Belgium
      1. Tom Van de Wiele
      1. Ghent University, Belgium
        1. Yves Guiot
        1. Université catholique de Louvain, Belgium
          1. Amandine Everard
          1. Université catholique de Louvain, Belgium
            1. Olivier Rottier
            1. Université catholique de Louvain, Belgium
              1. Lucie Geurts
              1. Université catholique de Louvain, Belgium
                1. Damien Naslain
                1. Université catholique de Louvain, Belgium
                  1. Audrey M Neyrinck
                  1. Université catholique de Louvain, Belgium
                    1. Didier M Lambert
                    1. Université catholique de Louvain, Belgium
                      1. Giulio G Muccioli
                      1. Université catholique de Louvain, Belgium
                        1. Nathalie M Delzenne (nathalie.delzenne{at}uclouvain.be)
                        1. Université catholique de Louvain, Belgium

                          Abstract

                          Background and aims: Obese and diabetic mice display enhanced intestinal permeability, metabolic endotoxaemia and low-grade inflammation that participate to 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, thereby improving inflammation and metabolic disorders during obesity and diabetes.

                          Methods: Ob/ob mice (Ob-CT) were treated with either prebiotic-fermentable carbohydrates (Ob-OFS) or non-prebiotic non-fermentable carbohydrates as control (Ob-Cell). Changes in the gut microbiota were assessed by DGGE and qPCR. Intestinal permeability was measured using the oral dextran-FITC challenge, plasma LPS levels, and intestinal epithelial tight-junction proteins ZO1 and Occludin (qPCR and immunohistochemistry). Plasma cytokines and gut-peptides were analyzed using a Multiplex-assay.

                          Results: As compared to controls (Ob-CT and Ob-Cell), Ob-OFS mice exhibited a lower intestinal permeability and an improved tight-junction integrity compared to controls. This was associated with a dramatically decreased inflammatory tone (lower plasma LPS and cytokines, decreased hepatic expression of inflammatory and oxidative stress markers). OFS feeding significantly increases portal plasma GLP-2 levels as well as its precursor, the proglucagon mRNA, in the jejunum and colon. Finally, a chronic infusion with GLP-2 mimicked most of the prebiotic treatment effects.

                          Conclusion: Gut microbiota participates to the inflammatory phenotype of ob/ob mice. Prebiotic-induced changes in gut microbiota improve intestinal permeability and inflammatory markers through a GLP-2-driven mechanism, contributing to the improvement of gut barrier functions during obesity and diabetes.

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