Effects of Gliadin Consumption
on the Intestinal Microbiota and
Metabolic Homeostasis in Mice Fed
a High-fat Diet
Li Zhang1,2,*, Daniel Andersen3,*, Henrik Munch Roager1, Martin Iain Bahl1,
Camilla Hartmann Friis Hansen2, Niels Banhos Danneskiold-Samsøe3,4, Karsten Kristiansen4,
Ilinca Daria Radulescu3, Christian Sina5, Henrik Lauritz Frandsen1, Axel Kornerup Hansen2,
Susanne Brix3, Lars I. Hellgren3 & Tine Rask Licht1
1National Food Institute, Technical University of Denmark, 2860 Søborg, Denmark.
2Department of Veterinary
Disease Biology, University of Copenhagen, 1871 Frederiksberg C, Denmark.
3Department of Systems Biology,
Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
4Department of Biology, University of Copenhagen,
2100 København Ø, Denmark.
5Department of Internal Medicine I, University Hospital of Schleswig-Holstein,
Lübeck, Germany.
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 gliadinfree,
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.
Scientific Reports doi: 10.1038/srep44613