Early‐life exposure to gut microbiota from disease‐protected mice does not impact disease outcome in type 1 diabetes susceptible NOD mice

Abstract

The microbial community making up the gut microbiota can profoundly influence intestinal homeostasis and immune system development, and is believed to influence the development of complex diseases including type 1 diabetes (T1D). T1D susceptible nonobese diabetic (NOD) mice have been shown to harbor a distinct microbiota to disease-protected mice. We hypothesized that the T1D susceptible genetic background of NOD mice would be resistant to the introduction of a C57BL/6-derived microbiota. NOD and C57BL/6 mice were cohoused either continually from birth, from birth until weaning or from weaning onwards, allowing transfer of microbiota between the mice. Cohousing NOD with C57BL/6 mice from before birth, resulted in moderate changes to the gut microbiota, whereas initiating cohousing at weaning only led to minimal changes. Terminating cohousing at weaning reduced the changes in the microbiota composition. However, diabetes onset was not significantly delayed and there was no reduction in intestinal inflammation or the proportion of regulatory T cells in the cohoused NOD mice. However, insulin but not islet-specific glucose-6-phosphatase catalytic subunit-related protein-specific CD8 T cells were reduced by cohousing suggesting an epitope-specific modulation of the autoreactive response by the gut microbiota. These results suggest that the T1D susceptible genetic background of the NOD mouse was resistant to the introduction of a C57BL/6-derived microbiota.

Immunological partners: the gut microbiome in homeostasis and disease

“…These reviews highlight the potential of targeted microbiome interventions in the treatment of stroke or to maximize vaccine efficacy. Finally, studies by Poyntz et al and Mullaney et al examine the individual contributions of genetic factors versus microbiota in experimental models of antibody responsiveness 11 or autoimmunity, 12 and find that in these instances, the microbiome cannot overcome genetic susceptibility.…”

“…Taken together, this collection of articles and editorials from Immunology [1][2][3][4][5][6] and Immunology & Cell Biology [7][8][9][10][11][12][13] begin to dissect the complex partnership that has evolved, and continues to evolve, between microbes and humans. The consequences of an unhealthy relationship (i.e.…”

A joint spotlight on research into the microbial immunity: beyond mere correlations

“…Six articles from each journal are featured in this Virtual Issue. [1][2][3][4][5][6][7][8][9][10][11][12] We will highlight the ICB articles here. The companion articles in Immunology are described in our accompanying Editorial in Immunology.…”

“…The companion articles in Immunology are described in our accompanying Editorial in Immunology. 13 The ICB articles cover a wide range of topics, from reviews describing mechanistic interactions with components of the immune system, 1,2 through original articles describing novel molecular interactions with the microbiota and their influence on inflammation 3 and vaccine responses, 4 to investigations of the relationships between the microbiota and diabetes in NOD mice, 5 and in patients with stroke. 6 Two of the ICB articles are reviews discussing interactions between the host, the microbiota and pathogenic microorganisms.…”

“…We include two examples in this series. 4,5 First, Poyntz et al examine the antibody response to immunization in substrains of BALB/c mice and find that changes in the intestinal microbiota do not affect the substrains' different antibody response phenotypes ( Figure 1④). 4 Instead, they identify genetic polymorphisms affecting isotype class-switching that are differentially expressed in mice from different vendors.…”