Department of Gastroenterology and Hepatology (Celiac Disease), Mayo Clinic, Rochester, MN, USA.
Department of Immunology, Mayo Clinic, Rochester, MN, USA.
BMC Microbiol. 2022 Jan 4;22(1):8. doi: 10.1186/s12866-021-02406-9.
Type 1 diabetes (T1D) is an autoimmune disease that is increasing in prevalence worldwide. One of the contributing factors to the pathogenesis of T1D is the composition of the intestinal microbiota, as has been demonstrated. in T1D patients, with some studies demonstrating a deficiency in their levels of Prevotella. We have isolated a strain of Prevotella histicola from a duodenal biopsy that has anti-inflammatory properties, and in addition, alters the development of autoimmune diseases in mouse models. Therefore, our hypothesis is that the oral administration of P. histicola might delay the development of T1D in the non-obese diabetic (NOD) mice. To assess this, we used the following materials and methods. Female NOD mice (ages 5-8 weeks) were administered every other day P. histicola that was cultured in-house. Blood glucose levels were measured every other week. Mice were sacrificed at various time points for histopathological analysis of the pancreas. Modulation of immune response by the commensal was tested by analyzing regulatory T-cells and NKp46+ cells using flow cytometry and intestinal cytokine mRNA transcript levels using quantitative RT-PCR. For microbial composition, 16 s rRNA gene analysis was conducted on stool samples collected at various time points.
Administration of P. histicola in NOD mice delayed the onset of T1D. Beta diversity in the fecal microbiomes demonstrated that the microbial composition of the mice administered P. histicola was different from those that were not treated. Treatment with P. histicola led to a significant increase in regulatory T cells with a concomitant decrease in NKp46+ cells in the pancreatic lymph nodes as compared to the untreated group after 5 weeks of treatment.
These observations suggest that P. histicola treatment delayed onset of diabetes by increasing the levels of regulatory T cells in the pancreatic lymph nodes. This preliminary work supports the rationale that enteral exposure to a non pathogenic commensal P. histicola be tested as a future therapy for T1D.
1 型糖尿病（T1D）是一种在全球范围内发病率不断上升的自身免疫性疾病。一些研究表明，肠道微生物群落的组成是 T1D 发病机制的一个促成因素，在 T1D 患者中，某些研究表明其普雷沃氏菌水平存在不足。我们从十二指肠活检中分离出一株具有抗炎特性的普雷沃氏菌Histicola 株，此外，它还改变了小鼠模型中自身免疫性疾病的发展。因此，我们的假设是，口服普雷沃氏菌Histicola 可能会延缓非肥胖型糖尿病（NOD）小鼠 T1D 的发展。为了评估这一点，我们使用了以下材料和方法。将每 2 天接受一次体内培养的普雷沃氏菌Histicola 治疗的雌性 NOD 小鼠（年龄 5-8 周）用于实验。每隔一周测量一次血糖水平。在不同时间点处死小鼠，对胰腺进行组织病理学分析。通过流式细胞术分析调节性 T 细胞和 NKp46+细胞，以及使用定量 RT-PCR 分析肠道细胞因子 mRNA 转录水平，来测试共生菌对免疫反应的调节作用。通过收集不同时间点的粪便样本进行 16s rRNA 基因分析来检测微生物组成。
在 NOD 小鼠中给予普雷沃氏菌Histicola 可延迟 T1D 的发病。粪便微生物组的β多样性表明，给予普雷沃氏菌Histicola 的小鼠的微生物组成与未治疗的小鼠不同。与未治疗组相比，治疗 5 周后，普雷沃氏菌Histicola 治疗组胰腺淋巴结中的调节性 T 细胞显著增加，同时 NKp46+细胞减少。
这些观察结果表明，普雷沃氏菌Histicola 治疗通过增加胰腺淋巴结中调节性 T 细胞的水平来延迟糖尿病的发作。这项初步工作支持了这样一种理念，即通过肠道暴露于非致病性共生菌普雷沃氏菌Histicola 作为 T1D 的未来治疗方法进行测试。
