TY - JOUR

T1 - Gluten-free diet during pregnancy alleviates signs of diabetes and celiac disease in NOD mouse offspring

AU - Haupt-Jorgensen, Martin

AU - Larsen, Jesper

AU - Josefsen, Knud

AU - Jørgensen, Tina Z.

AU - Antvorskov, Julie Christine

AU - Hansen, Axel K.

AU - Buschard, Karsten

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - beta-cell

KW - celiac disease

KW - gluten-free diet

KW - islet of Langerhans

KW - NOD mice

KW - type 1 diabetes

U2 - 10.1002/dmrr.2987

DO - 10.1002/dmrr.2987

M3 - Journal article

C2 - 29392873

AN - SCOPUS:85046373339

VL - 34

JO - Diabetes/Metabolism Research and Reviews

JF - Diabetes/Metabolism Research and Reviews

SN - 1520-7552

IS - 4

M1 - e2987

ER -