Shenzhen 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.
Institute for Cellular Therapeutics, Allegheny-Singer Research Institute, Pittsburgh, PA.
Transplantation. 2021 Sep 1;105(9):1980-1988. doi: 10.1097/TP.0000000000003603.
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.
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.
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.
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.
1 型糖尿病（T1DM）是一种慢性自身免疫性疾病，其特征是 T 细胞介导的胰岛β细胞破坏。有证据表明，T1DM 患者和用于特定糖尿病模型的小鼠都表现出肠道微生物群的变化，而失调的微生物群有助于 T1DM 的发病机制。胰岛移植（Tx）有望在 T1DM 的治疗中发挥重要作用。然而，用胰岛 Tx 治疗 T1DM 是否能纠正失调的微生物群尚不清楚。
在本研究中，我们用链脲佐菌素诱导糖尿病 C57BL/6 小鼠。然后对糖尿病小鼠进行胰岛素治疗或同种异体或同种异体细胞 Tx 治疗。从粪便颗粒中分离总 DNA，并使用高通量 16S rRNA 测序来研究肠道微生物群组成。
非糖尿病（未用链脲佐菌素处理）和糖尿病小鼠之间的总体微生物多样性无差异。我们的结果表明，非糖尿病和糖尿病小鼠之间的拟杆菌门与厚壁菌门的比例有显著差异。Tx 或胰岛素治疗部分纠正了失调的细菌组成。在属水平上，拟杆菌属、恶臭菌属和双歧杆菌属与疾病的进展和治疗效果有关，它们可能被用作预测 T1DM 患者治疗效果的生物标志物。
总之，我们的结果表明，糖尿病小鼠表现出微生物群组成的改变，用胰岛素和胰岛 Tx 治疗可以部分纠正失调的微生物群。
