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Gluten‐free diet during pregnancy alleviates signs of diabetes and celiac disease in NOD mouse offspring
Author(s) -
HauptJorgensen Martin,
Larsen Jesper,
Josefsen Knud,
Jørgensen Tina Z.,
Antvorskov Julie Christine,
Hansen Axel K.,
Buschard Karsten
Publication year - 2018
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.2987
Subject(s) - offspring , nod mice , medicine , endocrinology , diabetes mellitus , in utero , insulitis , pregnancy , nod , type 1 diabetes , islet , gluten free , immunology , biology , disease , fetus , genetics
Background Gluten‐free (GF) diet during pregnancy ameliorates autoimmune diabetes in nonobese diabetic (NOD) mouse offspring. Due to comorbidity of celiac disease in type 1 diabetes, we hypothesized that GF diet in utero alleviates the humoral and histopathological signs of celiac disease in NOD mice. We aimed to establish the mechanisms behind the diabetes‐protective effect of GF diet in utero. Methods Breeding pairs of NOD mice were fed a GF or gluten‐containing standard (STD) diet until parturition. The offspring were nursed by mothers on STD diet and continued on this diet until ages 4 and 13 weeks. Analyses of serum antitissue transglutaminase (anti‐tTG) intestine and islet histology, islet transglutaminase (TG) activity, and cytokine expression in T cells from lymphoid organs were performed. Results GF versus STD diet in utero led to reduced serum anti‐tTG titre and increased villus‐to‐crypt ratio at both ages. Insulitis along with systemic and local inflammation were decreased, but islet TG activity was unchanged in 13‐week‐old GF mice. These mice had unchanged beta‐cell volumes, but increased islet numbers throughout the prediabetic period. Conclusions Collectively, GF diet administered during pregnancy improves signs of celiac disease and autoimmune diabetes in the offspring. The diabetes‐ameliorative effect of GF diet in utero is followed by dampening of inflammation, unchanged beta‐cell volume, but increased islet numbers.