title: Effects of Gliadin consumption on the Intestinal Microbiota and Metabolic Homeostasis in Mice Fed a High-fat Diet.
abstract: Dietary gluten causes severe disorders like celiac disease in gluten-intolerant humans. However, currently understanding of its impact in tolerant individuals is limited. Our objective was to test whether gliadin, one of the detrimental parts of gluten, would impact the metabolic effects of an obesogenic diet. Mice were fed either a defined high-fat diet (HFD) containing 4% gliadin (n = 20), or a gliadin-free, isocaloric HFD (n = 20) for 23 weeks. Combined analysis of several parameters including insulin resistance, histology of liver and adipose tissue, intestinal microbiota in three gut compartments, gut barrier function, gene expression, urinary metabolites and immune profiles in intestinal, lymphoid, liver and adipose tissues was performed. Mice fed the gliadin-containing HFD displayed higher glycated hemoglobin and higher insulin resistance as evaluated by the homeostasis model assessment, more hepatic lipid accumulation and smaller adipocytes than mice fed the gliadin-free HFD. This was accompanied by alterations in the composition and activity of the gut microbiota, gut barrier function, urine metabolome, and immune phenotypes within liver and adipose tissue. Our results reveal that gliadin disturbs the intestinal environment and affects metabolic homeostasis in obese mice, suggesting a detrimental effect of gluten intake in gluten-tolerant subjects consuming a high-fat diet.
authors.affiliation: National Food Institute, Technical University of Denmark, 2860 Søborg, Denmark.|Department of Veterinary Disease Biology, University of Copenhagen, 1871 Frederiksberg C, Denmark.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Systems Biology, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
authors.forename: Daniel
authors.initials: D
authors.lastname: Andersen
authors.affiliation: National Food Institute, Technical University of Denmark, 2860 Søborg, Denmark.
authors.forename: Henrik Munch
authors.initials: HM
authors.lastname: Roager
authors.affiliation: National Food Institute, Technical University of Denmark, 2860 Søborg, Denmark.
authors.forename: Martin Iain
authors.initials: MI
authors.lastname: Bahl
authors.affiliation: Department of Veterinary Disease Biology, University of Copenhagen, 1871 Frederiksberg C, Denmark.
authors.forename: Camilla Hartmann Friis
authors.initials: CH
authors.lastname: Hansen
authors.affiliation: Department of Systems Biology, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.|Department of Biology, University of Copenhagen, 2100 København Ø, Denmark.
authors.forename: Niels Banhos
authors.initials: NB
authors.lastname: Danneskiold-Samsøe
authors.affiliation: Department of Biology, University of Copenhagen, 2100 København Ø, Denmark.
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.affiliation: Department of Systems Biology, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
authors.forename: Ilinca Daria
authors.initials: ID
authors.lastname: Radulescu
authors.affiliation: Department of Internal Medicine I, University Hospital of Schleswig-Holstein, Lübeck, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Sina
authors.affiliation: National Food Institute, Technical University of Denmark, 2860 Søborg, Denmark.
authors.forename: Henrik Lauritz
authors.initials: HL
authors.lastname: Frandsen
authors.affiliation: Department of Veterinary Disease Biology, University of Copenhagen, 1871 Frederiksberg C, Denmark.
authors.forename: Axel Kornerup
authors.initials: AK
authors.lastname: Hansen
authors.affiliation: Department of Systems Biology, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
authors.forename: Susanne
authors.initials: S
authors.lastname: Brix
authors.affiliation: Department of Systems Biology, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
authors.forename: Lars I
authors.initials: LI
authors.lastname: Hellgren
authors.affiliation: National Food Institute, Technical University of Denmark, 2860 Søborg, Denmark.
authors.forename: Tine Rask
authors.initials: TR
authors.lastname: Licht
mesh_terms: D017667:Adipocytes / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D048429:Cell Size; D059305:Diet, High-Fat; D000069196:Gastrointestinal Microbiome; D005786:Gene Expression Regulation; D005903:Gliadin / Q000008:administration & dosage*; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D007249:Inflammation / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007422:Intestines / Q000382:microbiology / Q000473:pathology; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D055442:Metabolome; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D010641:Phenotype; D014556:Urine
chemical_list: D018836:Inflammation Mediators; D005903:Gliadin; D005947:Glucose