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

King C, Sarvetnick N - PLoS ONE (2011)

Bottom Line: 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].However, evidence supporting this influential concept is surprisingly limited [12].By contrast, a spontaneous monoculture with a gram-positive aerobic spore-forming rod delayed the onset and reduced the incidence of diabetes.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, The Scripps Research Institute, La Jolla, California, United States of America. c.king@garvan.org.au

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.

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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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pone-0017049-g001: 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.

Mentions: We sought to determine the influence of intestinal microbiota on the incidence of type-1 diabetes in NOD mice. To our surprise, the incidence of type-1 diabetes in female germ free NOD mice (n = 22) was indistinguishable from that of NOD mice housed under SPF conditions in our colony (n = 20) (Figure 1, p>0.6696) or the 80% incidence of female NOD mice housed under SPF conditions at Taconic (Figure 1, p<0.78). However, our findings also indicated that intestinal microflora had the capacity to influence the development of type-1 diabetes. In one cohort of NOD mice (n = 22) housed in a separate isolator, a spontaneous contamination with a gram-positive aerobic spore-forming rod (that was subsequently typed as Bacillus cereus) was detected at week 16. These mice exhibited a delayed onset, and reduced incidence of clinical disease (p<0.001) during the 30-week study period (Figure 1).


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

King C, Sarvetnick N - PLoS ONE (2011)

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.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3045412&req=5

pone-0017049-g001: 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.
Mentions: We sought to determine the influence of intestinal microbiota on the incidence of type-1 diabetes in NOD mice. To our surprise, the incidence of type-1 diabetes in female germ free NOD mice (n = 22) was indistinguishable from that of NOD mice housed under SPF conditions in our colony (n = 20) (Figure 1, p>0.6696) or the 80% incidence of female NOD mice housed under SPF conditions at Taconic (Figure 1, p<0.78). However, our findings also indicated that intestinal microflora had the capacity to influence the development of type-1 diabetes. In one cohort of NOD mice (n = 22) housed in a separate isolator, a spontaneous contamination with a gram-positive aerobic spore-forming rod (that was subsequently typed as Bacillus cereus) was detected at week 16. These mice exhibited a delayed onset, and reduced incidence of clinical disease (p<0.001) during the 30-week study period (Figure 1).

Bottom Line: 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].However, evidence supporting this influential concept is surprisingly limited [12].By contrast, a spontaneous monoculture with a gram-positive aerobic spore-forming rod delayed the onset and reduced the incidence of diabetes.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, The Scripps Research Institute, La Jolla, California, United States of America. c.king@garvan.org.au

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.

Show MeSH
Related in: MedlinePlus