Genes and Environment in Diabetes Mellitus : A multi-species approach

1型糖尿病(T1D)影响着英国超过40万人，其中包括多达3万名儿童。治疗需要终生每天注射胰岛素，这种疾病是由遗传和环境因素引起的，这些因素会导致免疫系统破坏胰腺中正常产生胰岛素的细胞。该项目旨在更多地了解1型糖尿病(T1D)所涉及的风险因素，特别是是否有可能通过改变环境来降低T1D的风险。自20世纪50年代以来，T1D的发病率一直在逐年上升，恰逢儿童感染更频繁地使用抗生素。一种理论认为，抗生素会破坏肠道微生物(即微生物群)的平衡。已知微生物群参与免疫系统的发育，健康的微生物群被认为参与预防T1D的发育。对受T1D影响的儿童的微生物组的研究表明，与未患T1D的儿童相比，微生物的类型、频率和多样性有许多不同。T1D的小鼠模型，如NOD(非肥胖糖尿病)小鼠，也证明了抗生素的使用与T1D风险之间的关系。此外，最近的证据表明，一种名为Dexi的基因可能参与了微生物组的发育，以及T1D风险。这项建议将研究微生物组、Dexi基因和T1D风险之间的关系。在NOD模型中，将通过观察整个生命过程中粪便中微生物的遗传物质来检查微生物群。还将探讨具有功能或非功能的Dexi基因对微生物组的影响。此外，还将探讨改善微生物组健康的措施对T1D发展的影响。此外，还将探索一种研究微生物组与糖尿病发展的新模型。宠物狗可以像年轻人一样患上自发性胰岛素依赖型糖尿病，重要的是，它们比NOD模型更有优势，因为它们与我们的环境相同。这项研究还将使用大型兽医数据库来评估抗生素使用对宠物狗患糖尿病风险的影响。此外，将从在兽医医院接受新诊断糖尿病治疗的宠物狗以及非糖尿病狗身上收集粪便样本，以确定微生物群和糖尿病之间的关系是否与儿童一样存在于狗身上。最后，我们将探讨Dexi在人体免疫系统中的作用。将开发检测血液样本和免疫系统中Dexi蛋白的新方法，以便在未来探索Dexi、微生物组和人类免疫系统发育之间的关系。

Type 1 diabetes (T1D) affects more than 400,000 people in the UK including up to 30,000 children. Treatment involves lifelong daily insulin injections and the disease arises as the result of genetic and environmental factors, which cause the immune system to destroy the cells in the pancreas which normally produce insulin. This project is aimed at understanding more about the risk factors involved in type 1 diabetes (T1D) and in particular whether it might be possible to reduce the risk of T1D by making environmental changes.The incidence of T1D has been rising year on year since the 1950s, coinciding with more frequent use of antibiotics for childhood infections. One theory is that antibiotics disrupt the balance of micro-organism in the gut (known as the microbiome). The microbiome is known to be involved in the development of the immune system and a healthy microbiome is thought to be involved in protecting against the development of T1D. Studies of the microbiome in children affected with T1D demonstrate many differences in the type, frequency and diversity of micro-organisms compared to the microbiome of children without T1D. Mouse models of T1D such as the NOD (non-obese diabetic) mouse have also demonstrated a relationship between antibiotic use and T1D risk. In addition, recent evidence has suggested that a gene called DEXI may be involved in microbiome development, as well as T1D risk. This proposal will examine the relationship between the microbiome, the DEXI gene and T1D risk. In the NOD model, the microbiome will be examine by looking at the genetic material from micro-organisms in the faeces, throughout the life course. The effect on the microbiome of of having an functional or non-functional Dexi gene will also be explored. In addition, the impact of measures to improve microbiome health on the development of T1D on this model will also be explored.In addition, a new model for studying the microbiome and diabetes development will be explored. Pet dogs can develop spontaneous insulin-dependent diabetes mellitus just like young humans and importantly they have the advantage over the NOD model that they share our environment. This study will also use a large veterinary database to assess the impact of antibiotic use on the risk of diabetes development in pet dogs. In addition, samples of faeces will be collected from pet dogs undergoing treatment for newly diagnosed diabetes in a veterinary hospital, as well as non-diabetic dogs to determine if the same relationship between microbiome and diabetes exists in dogs as in children. Finally, the role of DEXI in the human immune system will be explored. New methods of detection of the DEXI protein in blood samples and the immune system will be developed, to allow the relationship between DEXI, the microbiome and the development of the human immune system to be explored in future.