The Bartholin Institute, Department of Pathology, Rigshospitalet, Copenhagen N, Denmark.
The Bartholin Institute, Department of Pathology, Rigshospitalet, Copenhagen N, Denmark.
J Autoimmun. 2021 Aug;122:102674. doi: 10.1016/j.jaut.2021.102674. Epub 2021 Jun 25.
The etiopathogenesis of the autoimmune disease type 1 diabetes (T1D) is still largely unknown, however, both genetic and environmental factors contribute to the development of the disease. A major contact surface for environmental factors is the gastrointestinal (GI) tract, where barrier defects in T1D likely cause diabetogenic antigens to enter the body tissues, contributing to beta-cell autoimmunity. Human and animal research imply that increased intestinal permeability is an important disease determinant, although the underlying methodologies, interpretations and conclusions are diverse. In this review, an updated comprehensive overview on intestinal permeability in patients with T1D and animal models of T1D is provided in the categories: in vivo permeability, ex vivo permeability, zonulin, molecular permeability and blood markers. Across categories, there is consistency pointing towards increased intestinal permeability in T1D. In animal models of T1D, the intestinal permeability varies with age and strains implying a need for careful selection of method and experimental setup. Furthermore, dietary interventions that affect diabetes incidence in animal models does also impact the intestinal permeability, suggesting an association between increased intestinal permeability and T1D development.
自身免疫性疾病 1 型糖尿病（T1D）的发病机制仍不清楚，但遗传和环境因素都有助于该病的发生。环境因素的一个主要接触表面是胃肠道（GI）道，在 T1D 中，屏障缺陷可能导致致糖尿病抗原进入身体组织，导致β细胞自身免疫。人体和动物研究表明，肠道通透性增加是一个重要的疾病决定因素，尽管其潜在的方法、解释和结论是多种多样的。在这篇综述中，提供了 T1D 患者和 T1D 动物模型中肠道通透性的最新综合概述，分为：体内通透性、离体通透性、紧密连接蛋白、分子通透性和血液标志物。在各个类别中，都有一致性表明 T1D 患者的肠道通透性增加。在 T1D 的动物模型中，肠道通透性随年龄和菌株而变化，这意味着需要仔细选择方法和实验设置。此外，影响动物模型中糖尿病发病率的饮食干预也会影响肠道通透性，这表明肠道通透性增加与 T1D 发展之间存在关联。
