1型糖尿病的病因尚不清楚，这是电子游戏软件生物学助理教授Emrah Altindis和他所在领域的其他人希望找到帮助1型糖尿病的新方法的中心焦点.6 million Americans living with the chronic autoimmune disease, a group that is expected to increase to 5 million people by 2050.
虽然遗传学电子游戏正规平台已经确定突变会增加患1型糖尿病的风险, the gene pool alone cannot fully explain who is susceptible to the disease. Altindis和同事们一直在探索肠道微生物群的相互联系, the immune system, 胰腺正在寻找答案，并在潜在的途径上与疾病作斗争, which disables the body’s ability to regulate blood glucose levels.
In his latest work, Altindis和他的同事首次在动物模型中发现了一种可以加速1型糖尿病发病的肠道微生物, the team reported in the journal of the Proceedings of the National Academy of Sciences. Notably, 将他们的发现与1型糖尿病微生物组的测序数据进行比较表明，在早期接触这种细菌会增加患有1型糖尿病遗传风险的儿童患该疾病的风险.
Assistant Professor of Biology Emrah Altindis
“虽然有几项电子游戏正规平台表明肠道微生物与1型糖尿病发病之间存在关联, to our knowledge, we discovered the first bacterium that can enhance type 1 diabetes,” said Altindis. “结合我们对患1型糖尿病儿童的肠道微生物群数据的分析, 我们离了解肠道微生物群，特别是微生物之间的潜在联系又近了一步 Parabacteriodes distasonis—and this complex autoimmune disease.”
According to the Juvenile Diabetes Research Foundation (JDRF), there are 1.600万美国人患有这种慢性疾病，预计到2050年这一数字将增加到500万.
“Although we have known type 1 diabetes for thousands of years, its cause is unknown,” said Altindis, whose research is supported by the National Institutes of Health, G. Harold and Leila Y. Mathers Charitable Foundation, and JDRF. “虽然遗传学电子游戏正规平台已经确定了一些人类基因的突变会增加患1型糖尿病的风险, 单靠遗传学并不能完全解释全球发病率的上升, specifically in industrialized countries.”
电子游戏正规平台人员面临的一个核心问题是，是什么使人体免疫系统与自身对抗.
“免疫系统的主要作用是识别自我和非自我，并保护身体免受非自我的侵害,” Altindis said. “When this recognition system is impaired, 我们的免疫细胞不仅开始攻击外来细胞，也开始攻击我们自己的细胞. This impaired mechanism of immune system causes autoimmune diseases.”
最近的1型糖尿病肠道微生物组电子游戏正规平台发现，1型糖尿病患者肠道微生物组的组成与非1型糖尿病患者有显著差异.
However, 这些电子游戏正规平台并没有建立微生物群和1型糖尿病之间的因果关系. “In this study, 我们发现了一种肠道细菌，它可能与疾病的发病有关,” Altindis said.
When the immune system detects a foreign particle, it starts to produce proteins called antibodies to destroy it. In autoimmune diseases, 自身抗体和免疫细胞以人类蛋白质为目标，而胰岛素是1型糖尿病患者免疫系统的主要目标. Altindis and his colleagues have focused on molecular mimicry, 一种自身免疫性疾病的机制，其中与宿主蛋白结构相似的外来抗原可以改变疾病的发病机制.
“Based on the central role of insulin in type 1 diabetes autoimmunity, 我们假设1型糖尿病是由一种分子模仿机制引起的，在这种机制中，暴露于微生物胰岛素会刺激免疫系统对抗人类胰岛素,” Altindis said.
“There is more work to do, 然而，这项电子游戏正规平台和类似的电子游戏正规平台有可能指导我们开发新的工具, including vaccines, antibiotics, or probiotics, for the prevention and treatment of type 1 diabetes.”
Previously, Altindis和他的团队有了一个惊人的发现，他们发现病毒有类似胰岛素的蛋白质. In the latest project, they focused on an insulin region, specifically a peptide, or a chain of amino acids—known as the B chain of insulin, 或B:9-23，这是1型糖尿病患者免疫细胞的目标，并在不同的微生物中发现了该区域的模拟物.电子游戏正规平台小组假设，因为人类胰岛素B:9-23和微生物胰岛素B:9-23将非常相似, 免疫细胞无法区分两者的区别，对这种细菌B:9-23样肽的免疫反应将与胰岛素交叉反应，从而靶向并破坏产生胰岛素的细胞.
Based on the molecular mimicry hypothesis, the team identified 17 microbialpeptides very similar to insulin B:9-23. Testing them in immune cells obtained from type 1 diabetes patients, they identified one bacterial insulin B:9-23 mimic peptide in Parabacteriodes distasonis that can stimulate the immune cells specific to insulin. Using cellular and animal models of type 1 diabetes, Altindis和他的同事们表明，分子模仿可能会引发1型糖尿病.
Colonization of the gut microbiome with Parabacteriodes distasonis 通过增加不同组织的炎症增加1型糖尿病的发病率, specifically in the pancreas, in mice used in type 1 diabetes T1D research, 电子游戏正规平台小组在文章《电子游戏软件》中报道."
This bacterium is most likely present in the human gut, however, 该电子游戏正规平台表明，接触的时间对1型糖尿病的发展很重要. The team then re-analyzed published human gutmicrobiome data, obtained from the Broad Foundation’s DIABIMMUNE project, 为了证明三岁以下的儿童如果在早期接触到这种肽/细菌就容易患上1型糖尿病.
“我们的电子游戏正规平台结果分析了从269名婴儿肠道微生物组中获得的已发表的人类1型糖尿病微生物组数据, sampled from ages 0 to threeyears, supports our hypothesis that being exposed to this bacterium, and more specifically to this insulin B:9-23-like bacterial peptide, in the first three years of life is a potential risk factor,” said Altindis.
Identifying the presence of the peptide is a significant step, said Altindis, who collaborated on the project with C. Ronald Kahn, MD, of the Joslin Diabetes Center, 佛罗里达大学和贝纳罗亚电子游戏正规平台所的电子游戏正规平台人员说, and a BC team including post-doctoral researcher Khyati Girdhar, BC’s Flow Cytometry Lab Director Patrick Autissier, and undergraduate student researchers Claudia Brady and Amol Raisingani.
But there is much more work to be done, he added.
“在这项电子游戏正规平台中，我们发现人类免疫细胞对人类胰岛素B:9-23有特异性反应 P. distasonis peptide and that P. distasonis can enhance type 1 diabetes development in the the mouse model, we have to prove that this enhancement is directly related to the peptide,” Altindis said.
To prove that, Girdhar正在通过删除模拟肽来对细菌基因组进行突变，并将在动物模型上测试其效果, Altindis said. 该团队还将分析另一项更全面的1型糖尿病电子游戏正规平台，即TEDDY.
“If these studies support our findings, this will support our initial molecular mimicry mechanism,” Altindis said. “There is more work to do, 然而，这项电子游戏正规平台和类似的电子游戏正规平台有可能指导我们开发新的工具, including vaccines, antibiotics, or probiotics, for the prevention and treatment of type 1 diabetes.”
Ed Hayward | University Communications | September 2022