Abstract
Type 1 diabetes (T1D) is a progressive autoimmune disease in which the insulin-producing beta cells are destroyed by auto-reactive T cells. Recent studies suggest that microbiota are closely associated with disease development. We studied gut, oral and vaginal microbiota longitudinally in non-obese diabetic (NOD) mice. We showed that the composition of microbiota is very different at the different mucosal sites and between young and adult mice. Gut microbiota are more diverse than oral or vaginal microbiota and the changes were more evident in the mice before and after onset of diabetes. Using alpha-diversity, Gram-positive/Gram-negative ratio as well as the relative abundance of Bacteroidetes and Erysipelotrichaceae in the gut microbiota, at 8 weeks of age, we formulated a predictive algorithm for T1D development in a cohort of 63 female NOD mice. Using this algorithm, we obtained 80% accuracy of prediction of diabetes onset, in two independent experiments, totaling 29 mice, with Area Under the Curve of 0.776 by ROC analysis. Interestingly, we did not find differences in peripheral blood mononuclear cells of the mice at 8 weeks of age, regardless of later diabetes development. Our results suggest that the algorithm could potentially be used in early prediction of future T1D development.
Highlights
Type 1 diabetes (T1D) is a progressive autoimmune disease in which the insulin-producing beta cells in the pancreatic islets are destroyed by auto-reactive T cells
We found that gut microbiota from non-obese diabetic (NOD) mice at 8 weeks of age underwent the most significant changes, some of which can be used to predict diabetes development later in life with 80% accuracy
Using the analytical results from the gut microbiota, especially at the age of 8 weeks, we retrospectively examined the association with diabetes development in this cohort
Summary
Type 1 diabetes (T1D) is a progressive autoimmune disease in which the insulin-producing beta cells in the pancreatic islets are destroyed by auto-reactive T cells. Studies using NOD mice have made significant contributions to our understanding of immunopathogenesis, including the role of gut microbiota, in T1D development[9,10,11,12,13,14]. It is known that the gut microbiota provide nutrients to the hosts and coevolve with the host immune system. It is not clear when gut microbiota are altered to a composition that facilitates the autoimmune destruction of insulin-producing beta cells, which leads to T1D onset. We found that gut microbiota from NOD mice at 8 weeks of age underwent the most significant changes, some of which can be used to predict diabetes development later in life with 80% accuracy. Our ultimate goal is to apply these biomarkers to finding more effective means to prevent T1D
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