Gluten-free but also gluten-enriched (gluten+) diet prevent diabetes in NOD mice; the gluten enigma in type 1 diabetes.
BACKGROUND
Environmental factors such as nutrition or exposure to infections play a substantial role in the pathogenesis of type 1 diabetes (T1D). We have previously shown that gluten-free, non-purified diet largely prevented diabetes in non-obese diabetic (NOD) mice. In this study we tested hypothesis that early introduction of gluten-enriched (gluten+) diet may increase diabetes incidence in NOD mice.


METHODS
Standard, gluten-free, gluten+ modified Altromin diets and hydrolysed-casein-based Pregestimil diet were fed to NOD females and diabetes incidence was followed for 310 days. Insulitis score and numbers of gut mucosal lymphocytes were determined in non-diabetic animals.


RESULTS
A significantly lower diabetes incidence (p < 0.0001) was observed in NOD mice fed gluten-free diet (5.9%, n = 34) and Pregestimil diet (10%, n = 30) compared to mice on the standard Altromin diet (60.6%, n = 33). Surprisingly, gluten+ diet also prevented diabetes incidence, even at the level found with the gluten-free diet (p < 0.0001, 5.9%, n = 34). The minority of mice, which developed diabetes on all the three diabetes-protective (gluten+, gluten-free, Pregestimil) diets, did that slightly later compared to those on the standard diet. Lower insulitis score compared to control mice was found in non-diabetic NOD mice on the gluten-free, and to a lesser extent also gluten+ and Pregestimil diets. No substantial differences in the number of CD3(+), TCR-gammadelta(+), and IgA(+) cells in the small intestine were documented.


CONCLUSIONS
Gluten+ diet prevents diabetes in NOD mice at the level found with the non-purified gluten-free diet. Possible mechanisms of the enigmatic, dual effect of dietary gluten on the development of T1D are discussed.
Funda
David P
DP
Division of Immunology and Gnotobiology, Institute of Microbiology, Czech Academy of Sciences, Prague, Czech Republic. funda@biomed.cas.cz
Kaas
Anne
A
Tlaskalová-Hogenová
Helena
H
Buschard
Karsten
K
D000818:Animals; D017252:CD3 Complex / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D004032:Diet; D005260:Female; D020022:Genetic Predisposition to Disease; D005983:Glutens / Q000008:administration & dosage*; D007082:Ileum / Q000276:immunology; D007070:Immunoglobulin A / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D007515:Islets of Langerhans / Q000473:pathology; D007583:Jejunum / Q000276:immunology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis
D017252:CD3 Complex; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D016692:Receptors, Antigen, T-Cell, gamma-delta; D005983:Glutens