Contributors: MICrobiologie de l'ALImentation au Service de la Santé (MICALIS); Institut National de la Recherche Agronomique (INRA)-AgroParisTech; Pathogénie microbienne moléculaire; Institut Pasteur Paris (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM); Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)); Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Génotypage des Eucaryotes (Plate-Forme); Institut Pasteur Paris (IP); Nanyang Technological University Singapour; Institut des Maladies Métaboliques et Cardiovasculaires (I2MC); Université Toulouse III - Paul Sabatier (UT3); Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM); Université de Toulouse (UT); Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG); Swiss Institute of Bioinformatics Lausanne (SIB); Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL); Collège de France - Chaire Microbiologie et Maladies infectieuses; Collège de France (CdF (institution)); This work was supported in part by the Société Française de Nutrition; the Fondation des Treilles created by Anne Gruner Schlumberger (www.les-treilles.com); the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence “Integrative Biology of Emerging Infectious Diseases” (Grant ANR-10-LABX-62-IBEID); the European Research Council Advanced Grants 339579-DECRYPT (to P.J.S.); a Start-Up Grant from the Lee Kong Chian School of Medicine, Nanyang Technological University; and the 7th EU program TORNADO.; We thank Laurence Motreff for her help with the Illumina libraries preparation and the MiSeq run; Eeswari Paramalingam for animal handling and tissue preparation; Jacques Ravel for editing the manuscript; and Nathalie Bechon for her contribution during her fellowship. J.T. was in part funded by the Contrat Jeune Scientifique from the Institut National de la Recherche Agronomique (Jouy-en-Josas, France).; ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010); European Project: 339579,EC:FP7:ERC,ERC-2013-ADG,DECRYPT(2014)
نبذة مختصرة : International audience ; Diet is among the most important factors contributing to intestinal homeostasis, and basic functions performed by the small intestine need to be tightly preserved to maintain health. Little is known about the direct impact of high-fat (HF) diet on small-intestinal mucosal defenses and spatial distribution of the microbiota during the early phase of its administration. We observed that only 30 d after HF diet initiation, the intervillous zone of the ileum-which is usually described as free of bacteria-became occupied by a dense microbiota. In addition to affecting its spatial distribution, HF diet also drastically affected microbiota composition with a profile characterized by the expansion of Firmicutes (appearance of Erysipelotrichi), Proteobacteria (Desulfovibrionales) and Verrucomicrobia, and decrease of Bacteroidetes (family S24-7) and Candidatus arthromitus A decrease in antimicrobial peptide expression was predominantly observed in the ileum where bacterial density appeared highest. In addition, HF diet increased intestinal permeability and decreased cystic fibrosis transmembrane conductance regulator (Cftr) and the Na-K-2Cl cotransporter 1 (Nkcc1) gene and protein expressions, leading to a decrease in ileal secretion of chloride, likely responsible for massive alteration in mucus phenotype. This complex phenotype triggered by HF diet at the interface between the microbiota and the mucosal surface was reversed when the diet was switched back to standard composition or when mice were treated for 1 wk with rosiglitazone, a specific agonist of peroxisome proliferator-activated receptor-γ (PPAR-γ). Moreover, weaker expression of antimicrobial peptide-encoding genes and intervillous bacterial colonization were observed in Ppar-γ-deficient mice, highlighting the major role of lipids in modulation of mucosal immune defenses.
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