Introduction. Type 1 diabetes (T1D) is a chronic autoimmune disease in which destruction or damaging of the beta-cells in the islets of Langerhans in the pancreas results in insulin deficiency and hyperglycemia1-3. T1D usually starts in people younger than 30 and is therefore also termed juvenile-onset diabetes, even though it can occur at any age4. In the past few decades there has been a continuous rise in the incidence of T1D, which cannot be explained by genetic factors or diet alone3,4. Studies have found that NOD (non-obese diabetic) mice harbor gut microbes that induce diabetes and that their diabetogenic microbiome can be amplified early in life through antibiotic exposure5,6. Other studies show that human subjects with autoantibodies had different levels of the Firmicutes genera Lactobacillus and Staphylococcus compared with healthy controls with no family history of autoimmunity8,9. These findings could suggest a potential probiotic therapy for Type 1 Diabetes. Methods. The non-obese diabetic mouse model was utilized. Gut microbiota composition was analyzed in feces via 454/FLX Titanium pyro-sequencing. This was statistically correlated with diabetes onset age and immune cell numbers measured in diabetic and non-diabetic mice. Fecal matter from children with at least two autoantibodies and autoantibody-negative children were analyzed using pyrosequencing to determine composition. Subjects were matched for age, sex, early feeding history, and HLA risk genotype. Results. Mice without a gut microbiome had a metabolic profile similar to pre-diabetic children. The presence of probiotic bacteria in the gut increased the number and suppressive activity of regulatory T (Treg) cells, decreasing proinflammatory cells and indicating a deep impact of microbiota on immune homeostasis6. Studies show fecal gut microbiota collected at weaning showed significant differences in the early bacterial community composition between NOD mice later classified as diabetic or non-diabetic at 30 weeks of age7. An increased level of splenic Treg cells was associated with diabetes protection in the NOD mice. A microbiota signature characterized by a decrease in Bacteriodales, and Prevotella and an increase in Lachnospiraceae, Ruminococcus, and Oscillospira was associated with protection against diabetes8,9. Conclusions. Studies have found that NOD (non-obese diabetic) mice harbor gut microbes that induce diabetes and that their diabetogenic microbiome can be amplified early in life through antibiotic exposure. A microbiota signature characterized by a decrease in Bacteriodales, and Prevotella and an increase in Lachnospiraceae, Ruminococcus, and Oscillospira may contribute to T1D by decreasing FoxP3C Treg cells that protect against diabetes.
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- Krych Ł, Nielsen DS, Hansen AK, Hansen CH. Gut microbial markers are associated with diabetes onset, regulatory imbalance, and IFN-γ level in NOD mice. Gut Microbes. 2015;6(2):101-9.
- Peng J, Narasimhan S, Marchesi JR, Benson A, Wong FS, Wen L. Long term effect of gut microbiota transfer on diabetes development. J Autoimmun. 2014;53:85-94.
- De goffau MC, Luopajärvi K, Knip M, et al. Fecal microbiota composition differs between children with β-cell autoimmunity and those without. Diabetes. 2013;62(4):1238-44.
- Candon, S., Perez-Arroyo, A., Marquet, C., et al. Antibiotics in early life alter the gut microbiome and increase disease incidence in a spontaneous mouse model of autoimmune insulin-dependent diabetes. PLoS One. 2015;10(5).
- Boursi, B., Mamtani, R., Haynes, K., et al. The effect of past antibiotic exposure on diabetes risk. European Journal of Endocrinology. 2015;172(6):639-48.