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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