Effect of Early-life Gut Mucosal Compromise on Disease Progression in NOD Mice.

Disease expression in spontaneous nonobese diabetic (NOD) mice depends on environmental stimuli such as stress, diet, and gut microbiota composition. We evaluated a brief, early-life gut intervention in which pups were weaned to low-dose dextran sulfate sodium (DSS). We hypothesized that the mucus-reducing effect of this compound and subsequent increased host-bacterial contact would delay disease onset and decrease insulitis due to enhanced oral tolerance. However, disease incidence did not differ between groups, although median survival (time point when 50% of the mice are still alive) of the control group was 184 d compared with 205 d for DSS-treated mice. Mean age at disease onset (that is, blood glucose of at least 12 mmol/L) was 164 d for control mice and 159 d for DSS-treated mice. In addition, 62.5% of control mice reached a blood glucose of 12 mmol/L before 30 wk of age compared with 59% in DSS-treated mice, which had a significant transient increase in serum insulin in week 4. No changes were found in immune cells collected from spleen, pancreatic lymph nodes, and mesenteric lymph nodes. Although mice received a low dose of DSS, the subsequent reduction in the diversity of the microbiota during weeks 4 through 6 led to increased cecal length and weight and, in week 13, a tendency toward decreased colon length, with increased leakage of LPS to the blood. We conclude that mucus reduction and subsequent increased host-bacterial contact did not affect overall disease progression in NOD mice.

Diabetes preventive gluten-free diet decreases the number of caecal bacteria in non-obese diabetic mice.

BACKGROUND: A gluten-free diet reduces the incidence of diabetes mellitus in non-obese diabetic (NOD) mice, but the mechanism is not known. The aim of this study was to examine the possible influence of the diet on the caecal bacterial flora, which may affect the intestinal physiology and mediate disease prevention. METHODS: Two groups of NOD mice from the age of 3 weeks were fed either a gluten-free diet or a standard diet. Each diabetic mouse, when diagnosed, along with a non-diabetic mouse from the same diet group and two non-diabetic mice from the alternate diet group were euthanized and sampled for classical bacteriological examination. RESULTS: Nine out of 19 (47%) standard-fed mice and 1 out of 19 (5%) gluten-free-fed mice developed diabetes (p < 0.01). Mice on the gluten-free diet had significantly fewer aerobically (p < 0.01) and microaerophilically (p < 0.001) cultivated bacteria in their intestines than standard-fed mice. Non-diabetic mice also had significantly fewer microa erophilic and anaerobic bacteria than diabetic mice (p < 0.05). These differences were primarily due to a difference in the Gram-positive flora. CONCLUSIONS: The gluten-free diet compared to the standard diet both qualitatively and quantitatively substantially altered the composition of the caecal bacterial flora in NOD mice. Although Gram-positive bacteria might influence the beta cells through certain digestive products, it is more likely to assume that any effect on diabetes incidence is immunological.