Titre
High-fat diet modifies the PPAR-γ pathway leading to disruption of microbial and physiological ecosystem in murine small intestine.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Auteur(s)
Tomas, J.
Auteure/Auteur
Mulet, C.
Auteure/Auteur
Saffarian, A.
Auteure/Auteur
Cavin, J.B.
Auteure/Auteur
Ducroc, R.
Auteure/Auteur
Regnault, B.
Auteure/Auteur
Kun Tan, C.
Auteure/Auteur
Duszka, K.
Auteure/Auteur
Burcelin, R.
Auteure/Auteur
Wahli, W.
Auteure/Auteur
Sansonetti, P.J.
Auteure/Auteur
Pédron, T.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1091-6490
Statut éditorial
Publié
Date de publication
2016-10-04
Volume
113
Numéro
40
Première page
E5934
Dernière page/numéro d’article
E5943
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
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.
Sujets
PID Serval
serval:BIB_BE066FF5BB1F
PMID
Open Access
Oui
Date de création
2016-11-03T07:27:12.235Z
Date de création dans IRIS
2025-05-21T01:56:14Z
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Nom
PNAS-2016-Tomas-E5934-43.pdf
Version du manuscrit
published
Taille
1.27 MB
Format
Adobe PDF
PID Serval
serval:BIB_BE066FF5BB1F.P001
URN
urn:nbn:ch:serval-BIB_BE066FF5BB1F9
Somme de contrôle
(MD5):e1a41f14f670f07ea39171187a39b62f