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Controls of Hyperglycemia Improves Dysregulated Microbiota in Diabetic Mice
Mengtao Cao1, Yuanzheng Peng1, Ying Lu1
1Shenzhen Xenotransplantation Medical Engineering Research and Development Center, Institute of Translational Medicine, Shenzhen University Health Science Center, Shenzhen University School of Medicine, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.
Background:
Type 1 diabetes (T1DM) is a chronic autoimmune disease characterized by T-cell-mediated destruction of insulin-producing beta cells. Evidence shows that patients with T1DM and mice used in specific diabetic models both exhibit changes in their intestinal microbiota and dysregulated microbiota contributes to the pathogenesis of T1DM. Islet transplantation (Tx) is poised to play an important role in the treatment of T1DM. However, whether treatment of T1DM with islet Tx can rescue dysregulated microbiota remains unclear.
Methods:
In this study, we induced diabetic C57BL/6 mice with streptozotocin. Then treatment with either insulin administration, or homogenic or allogenic islet Tx was performed to the diabetic mice. Total DNA was isolated from fecal pellets and high-throughput 16S rRNA sequencing was used to investigate intestinal microbiota composition.
Results:
The overall microbial diversity was comparable between control (nonstreptozotocin treated) and diabetic mice. Our results showed the ratio of the Bacteroidetes: Firmicutes between nondiabetic and diabetic mice was significant different. Treatment with islet Tx or insulin partially corrects the dysregulated bacterial composition. At the genus level, Bacteroides, Odoribacter, and Alistipes were associated with the progression and treatment efficacy of the disease, which may be used as a biomarker to predict curative effect of treatment for patients with T1DM.
Conclusions:
Collectively, our results indicate that diabetic mice show changed microbiota composition and that treatment with insulin and islet Tx can partially correct the dysregulated microbiota.

