Kondrashova Anita, Hyöty Heikki
School of Medicine, University of Tampere , Tampere , Finland.
Int Rev Immunol. 2014 Jul-Aug;33(4):284-95. doi: 10.3109/08830185.2014.889130. Epub 2014 Mar 10.
Type 1 diabetes is caused by an immune-mediated destruction of insulin producing beta-cells in the pancreas. The risk of the disease is determined by interactions between more than 40 different susceptibility genes and yet unidentified environmental factors. The rapidly increasing incidence indicates that these environmental agents have a significant role in the pathogenesis. Microbes have associated with both increased and decreased risk reflecting their possible role as risk or protective factors. Two main hypotheses have been proposed to explain these effects: the hygiene hypothesis suggests that microbial exposures in early childhood stimulate immunoregulatory mechanisms which control autoimmune reactions (analogy with allergy), while the triggering hypothesis suggests that specific microbes damage insulin producing cells. Certain viruses, particularly enteroviruses, are currently the main candidates for such risk microbes. Enteroviruses cause diabetes in animals and have associated with increased risk of type 1 diabetes in epidemiological studies. They have also been detected in the pancreas of diabetic patients. Possible protective effect of microbes has been studied in animal models and in epidemiological studies, where certain enteral microbes (e.g. hepatitis A virus and Helicobacter pylori) and patterns of gut microbiome have associated with low risk of type 1 diabetes. In conclusion, these microbial effects offer attractive possibilities for the development of preventive interventions for type 1 diabetes based on the elimination of triggering agents (e.g. enterovirus vaccines) or use of protective microbes as probiotics.
1型糖尿病是由胰腺中产生胰岛素的β细胞受到免疫介导的破坏所致。该疾病的风险由40多种不同的易感基因与尚未明确的环境因素之间的相互作用决定。发病率的迅速上升表明这些环境因素在发病机制中起着重要作用。微生物与患病风险的增加和降低均有关联，这反映了它们可能作为风险因素或保护因素的作用。已提出两种主要假说来解释这些影响：卫生假说认为幼儿期接触微生物会刺激控制自身免疫反应的免疫调节机制（与过敏类似），而触发假说则认为特定微生物会损害产生胰岛素的细胞。某些病毒，尤其是肠道病毒，目前是这类风险微生物的主要候选者。肠道病毒可在动物中引发糖尿病，并且在流行病学研究中与1型糖尿病风险增加有关。在糖尿病患者的胰腺中也检测到了肠道病毒。已在动物模型和流行病学研究中对微生物的可能保护作用进行了研究，其中某些肠道微生物（如甲型肝炎病毒和幽门螺杆菌）以及肠道微生物群模式与1型糖尿病的低风险有关。总之，这些微生物效应为基于消除触发因素（如肠道病毒疫苗）或使用保护性微生物作为益生菌来开发1型糖尿病的预防性干预措施提供了诱人的可能性。
