The incidence of type-1 diabetes in NOD mice is modulated by restricted flora not germ-free conditions

Cecile King, Nora Sarvetnick, Cecile King, Nora Sarvetnick

Abstract

In the NOD mouse, the incidence of type-1 diabetes is thought to be influenced by the degree of cleanliness of the mouse colony. Studies collectively demonstrate that exposure to bacterial antigen or infection in the neonatal period prevents diabetes [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], supporting the notion that immunostimulation can benefit the maturation of the postnatal immune system [11]. A widely accepted extrapolation from this data has been the notion that NOD mice maintained under germ-free conditions have an increased incidence of diabetes. However, evidence supporting this influential concept is surprisingly limited [12]. In this study, we demonstrate that the incidence of diabetes in female NOD mice remained unchanged under germ-free conditions. By contrast, a spontaneous monoculture with a gram-positive aerobic spore-forming rod delayed the onset and reduced the incidence of diabetes. These findings challenge the view that germ-free NOD mice have increased diabetes incidence and demonstrate that modulation of intestinal microbiota can prevent the development of type-1 diabetes.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. The incidence of type-1 diabetes…
Figure 1. The incidence of type-1 diabetes in female NOD mice remains unchanged under germ-free conditions but is reduced by restricted flora.
Cumulative diabetes incidence of germ-free female NOD mice (NOD germ-free n = 22), female NOD mice monocolonized with an aerobic spore-forming bacteria (Bacillus cereus) detected at week 16 (NOD AerSFB n = 22) and female NOD mice housed under specific pathogen-free conditions (NOD SPF Scripps n = 22, NOD SPF Taconic n = 40). Urine glucose was measured every one or two weeks as shown and mice that had reached 4+ (55 mmol/L) were considered diabetic. There was a significant inhibition (p<0.001) in the incidence of diabetes in monocolonized NOD mice compared with SPF NOD mice, but no significant difference between germ free and SPF NOD mice (p>0.05), Anova.

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