Gluten-free diet prevents diabetes in NOD mice

Abstract

Background Epidemiological as well as animal studies have shown that environmental factors such as nutrition contribute to the development of diabetes. In this study we investigated whether the early introduction of a gluten‐free diet can influence the onset and/or incidence of diabetes, as well as insulitis and the number of gut mucosal lymphocytes, in non‐obese diabetic (NOD) mice. Methods Gluten‐free and standard Altromin diets (with the same milk protein and vitamin content) were given to breeding pairs of NOD mice as well as to the first generation of NOD female mice, which were then observed for 320 days. Results A substantially lower diabetes incidence (χ2=15.8, p=0.00007) was observed in NOD mice on the gluten‐free diet (15%, n=27) compared to mice on the standard diet (64%, n=28). In addition, mice on the gluten‐free diet developed diabetes significantly later (244±24 days SEM) compared to those on the standard diet (197±8 days, p=0.03). No differences in the number of CD3+, TCR‐γδ+, IgA+, and IgM+ cells in the small intestine were observed. Conclusion We showed that gluten‐free diet both delayed and to a large extent prevented diabetes in NOD mice that have never been exposed to gluten. Copyright © 1999 John Wiley & Sons, Ltd.

Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats

“…Among others, dietary proteins are possible triggers stimulating zonulin secretion (27), as also suggested by the observation that BBDP rats fed with hydrolyzed chow have a reduced incidence of T1D (13). In the NOD mouse model of T1D, gluten has been identified as a potential trigger of the autoimmune process (28). In CD, gluten causes increased secretion of zonulin, promoting increased intestinal permeability with continuous exposure of the GI immune system to gluten and other environmental antigens (27).…”

Wheat protein-induced proinflammatory T helper 1 bias in mesenteric lymph nodes of young diabetes-prone rats

“…Wheat gluten is a concentrated mixture of wheat proteins that is associated with the development of type 1 diabetes in BBdp rats [4,30,31] and NOD mice [5][6][7]54]. Feeding nutritionally comparable semipurified diets in which wheat gluten was either the major or the sole protein source to BBdp rats produced nearly three times as many cases of type 1 diabetes and higher insulitis rating compared with HC-fed rats (p<0.001) [4].…”

“…Approximately two-thirds of diabetes-prone BioBreeding (BBdp) rats from the Ottawa colony fed a defined wheat-based diet (NTP-2000) [3] develop type 1 diabetes between 65 and 130 days, whereas only 20-25% of BBdp rats fed a protective hydrolysed casein-based AIN-93G (HC) diet become diabetic [4]. Diabetes in non-obese diabetic (NOD) mice is also associated with wheat [1,[5][6][7]. Early exposure to cereals including wheat was the factor most strongly associated with the development of islet autoantibodies in two recent prospective studies in children at high risk of developing type 1 diabetes [8,9].…”

Antibiotic treatment partially protects against type 1 diabetes in the Bio-Breeding diabetes-prone rat. Is the gut flora involved in the development of type 1 diabetes?

“…Haematoxylin/eosin-stained paraffin sections of the pancreas were evaluated for insulitis as previously described [4].…”

“…Several mechanisms for the protective effects of the HC diet have been described, such as Th2 skewing, islet neogenesis and inhibition of hyperexpression of MHC class I on beta cells [2]. In addition, a diabetes-preventive gluten-free diet has been shown to decrease the number of caecal bacteria in non-obese diabetic mice, suggesting that such diets may also exert their protective effect by changing the intestinal flora [3,4].…”