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Inflammatory tendencies and overproduction of IL-17 in the colon of young NOD mice are counteracted with diet change.

Alam C, Valkonen S, Palagani V, Jalava J, Eerola E, Hänninen A - Diabetes (2010)

Bottom Line: Young NOD mice showed a disturbed tolerance to autologous commensal bacteria.Increased numbers of activated CD4 T-cells and (CD11b(+)CD11c(+)) dendritic cells and elevated levels of Th17 cells and IL23 mRNA were moreover observed in colon lamina propria.Disrupted immune tolerance in the distal intestine may influence peritoneal cell pools and B-cell-mediated activation of diabetogenic T-cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.

ABSTRACT

Objective: Dietary factors influence diabetes development in the NOD mouse. Diet affects the composition of microbiota in the distal intestine, which may subsequently influence intestinal immune homeostasis. However, the specific effects of antidiabetogenic diets on gut immunity and the explicit associations between intestinal immune disruption and type 1 diabetes onset remain unclear.

Research design and methods: Gut microbiota of NOD mice fed a conventional diet or ProSobee formula were compared using gas chromatography. Colonic lamina propria immune cells were characterized in terms of activation markers, cytokine mRNA and Th17 and Foxp3(+) T-cell numbers, using real-time PCR and flow cytometry. Activation of diabetogenic CD4 T-cells by purified B-cells was assessed in both groups. Immune tolerance to autologous commensal bacteria was evaluated in vitro using thymidine-incorporation tests.

Results: Young NOD mice showed a disturbed tolerance to autologous commensal bacteria. Increased numbers of activated CD4 T-cells and (CD11b(+)CD11c(+)) dendritic cells and elevated levels of Th17 cells and IL23 mRNA were moreover observed in colon lamina propria. These phenomena were abolished when mice were fed an antidiabetogenic diet. The antidiabetogenic diet also altered the expression levels of costimulatory molecules and the capacity of peritoneal B-cells to induce insulin-specific CD4 T-cell proliferation.

Conclusions: Young NOD mice show signs of subclinical colitis, but the symptoms are alleviated by a diet change to an antidiabetogenic diet. Disrupted immune tolerance in the distal intestine may influence peritoneal cell pools and B-cell-mediated activation of diabetogenic T-cells.

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Diabetes incidence and bacterial fatty acid composition for NOD and PNOD mice. A: Diabetes incidence for NOD mice that have been raised on conventional murine food (broken line) and on ProSobee (continuous line). n = 18 per group. B: Example of a cluster analysis of fatty acid profiles from the stool samples. All 16 samples are compared with each other and clustered accordingly. An index of 100 indicates complete similarity with the same fatty acids (peaks in the chromatogram) found in the same concentrations in the samples compared; an index of 0 indicates complete dissimilarity. C: GLC analysis of fecal bacterial fatty acids from NOD and PNOD mice. Each peak in the graph represents an individual fatty acid. Graphs are representative of NOD (top row) and PNOD (bottom row) at 3 weeks (left column), 5 weeks (middle column), and 10 weeks (right column). n = 13–17 mice per group.
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Figure 3: Diabetes incidence and bacterial fatty acid composition for NOD and PNOD mice. A: Diabetes incidence for NOD mice that have been raised on conventional murine food (broken line) and on ProSobee (continuous line). n = 18 per group. B: Example of a cluster analysis of fatty acid profiles from the stool samples. All 16 samples are compared with each other and clustered accordingly. An index of 100 indicates complete similarity with the same fatty acids (peaks in the chromatogram) found in the same concentrations in the samples compared; an index of 0 indicates complete dissimilarity. C: GLC analysis of fecal bacterial fatty acids from NOD and PNOD mice. Each peak in the graph represents an individual fatty acid. Graphs are representative of NOD (top row) and PNOD (bottom row) at 3 weeks (left column), 5 weeks (middle column), and 10 weeks (right column). n = 13–17 mice per group.

Mentions: Diabetes incidence was significantly lower in NOD mice that had been fed ProSobee instead of conventional food (Fig. 3A). The fatty acid profile of NOD and PNOD did not differ at 3 weeks of age (preweaning). However, at 5 and 10 weeks of age, GLC analysis revealed profound differences in the bacterial fatty acid profiles of NOD and PNOD gut bacteria (Fig. 3B and C).


Inflammatory tendencies and overproduction of IL-17 in the colon of young NOD mice are counteracted with diet change.

Alam C, Valkonen S, Palagani V, Jalava J, Eerola E, Hänninen A - Diabetes (2010)

Diabetes incidence and bacterial fatty acid composition for NOD and PNOD mice. A: Diabetes incidence for NOD mice that have been raised on conventional murine food (broken line) and on ProSobee (continuous line). n = 18 per group. B: Example of a cluster analysis of fatty acid profiles from the stool samples. All 16 samples are compared with each other and clustered accordingly. An index of 100 indicates complete similarity with the same fatty acids (peaks in the chromatogram) found in the same concentrations in the samples compared; an index of 0 indicates complete dissimilarity. C: GLC analysis of fecal bacterial fatty acids from NOD and PNOD mice. Each peak in the graph represents an individual fatty acid. Graphs are representative of NOD (top row) and PNOD (bottom row) at 3 weeks (left column), 5 weeks (middle column), and 10 weeks (right column). n = 13–17 mice per group.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2927946&req=5

Figure 3: Diabetes incidence and bacterial fatty acid composition for NOD and PNOD mice. A: Diabetes incidence for NOD mice that have been raised on conventional murine food (broken line) and on ProSobee (continuous line). n = 18 per group. B: Example of a cluster analysis of fatty acid profiles from the stool samples. All 16 samples are compared with each other and clustered accordingly. An index of 100 indicates complete similarity with the same fatty acids (peaks in the chromatogram) found in the same concentrations in the samples compared; an index of 0 indicates complete dissimilarity. C: GLC analysis of fecal bacterial fatty acids from NOD and PNOD mice. Each peak in the graph represents an individual fatty acid. Graphs are representative of NOD (top row) and PNOD (bottom row) at 3 weeks (left column), 5 weeks (middle column), and 10 weeks (right column). n = 13–17 mice per group.
Mentions: Diabetes incidence was significantly lower in NOD mice that had been fed ProSobee instead of conventional food (Fig. 3A). The fatty acid profile of NOD and PNOD did not differ at 3 weeks of age (preweaning). However, at 5 and 10 weeks of age, GLC analysis revealed profound differences in the bacterial fatty acid profiles of NOD and PNOD gut bacteria (Fig. 3B and C).

Bottom Line: Young NOD mice showed a disturbed tolerance to autologous commensal bacteria.Increased numbers of activated CD4 T-cells and (CD11b(+)CD11c(+)) dendritic cells and elevated levels of Th17 cells and IL23 mRNA were moreover observed in colon lamina propria.Disrupted immune tolerance in the distal intestine may influence peritoneal cell pools and B-cell-mediated activation of diabetogenic T-cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.

ABSTRACT

Objective: Dietary factors influence diabetes development in the NOD mouse. Diet affects the composition of microbiota in the distal intestine, which may subsequently influence intestinal immune homeostasis. However, the specific effects of antidiabetogenic diets on gut immunity and the explicit associations between intestinal immune disruption and type 1 diabetes onset remain unclear.

Research design and methods: Gut microbiota of NOD mice fed a conventional diet or ProSobee formula were compared using gas chromatography. Colonic lamina propria immune cells were characterized in terms of activation markers, cytokine mRNA and Th17 and Foxp3(+) T-cell numbers, using real-time PCR and flow cytometry. Activation of diabetogenic CD4 T-cells by purified B-cells was assessed in both groups. Immune tolerance to autologous commensal bacteria was evaluated in vitro using thymidine-incorporation tests.

Results: Young NOD mice showed a disturbed tolerance to autologous commensal bacteria. Increased numbers of activated CD4 T-cells and (CD11b(+)CD11c(+)) dendritic cells and elevated levels of Th17 cells and IL23 mRNA were moreover observed in colon lamina propria. These phenomena were abolished when mice were fed an antidiabetogenic diet. The antidiabetogenic diet also altered the expression levels of costimulatory molecules and the capacity of peritoneal B-cells to induce insulin-specific CD4 T-cell proliferation.

Conclusions: Young NOD mice show signs of subclinical colitis, but the symptoms are alleviated by a diet change to an antidiabetogenic diet. Disrupted immune tolerance in the distal intestine may influence peritoneal cell pools and B-cell-mediated activation of diabetogenic T-cells.

Show MeSH
Related in: MedlinePlus