The cause of type 1 diabetes remains unknown and is a central focus of 电子游戏软件 生物学助理教授Emrah Altindis and others in his field hoping to find new ways to help 1.600万美国人患有慢性自身免疫性疾病, 到2050年，这一群体预计将增加到500万.
While genetics studies have identified mutations that increase the risk of developing type 1 diabetes, 仅凭基因库并不能完全解释谁易患这种疾病. Altindis and colleagues have been probing the interconnectedness of gut microbiota, 免疫系统, and the pancreas in the search for answers and a lead on potential paths to combat the disease, 它会使身体失去调节血糖水平的能力.
在他最近的作品中, Altindis and his colleagues for the first time identified a gut microbe that can accelerate type 1 diabetes onset in an animal model, 这个团队 报道 在杂志上 美国国家科学院院刊. 值得注意的是, comparing their findings to a clearinghouse of sequencing data for the type 1 diabetes microbiome indicates that exposure to this bacterium at an early age increases the risk to develop type 1diabetes in children at genetic risk of the disease.
生物学助理教授Emrah Altindis
“While there are several studies indicating associations between gut microbes and type 1 diabetes onset, 据我们所知, 我们发现了第一个可以增加1型糖尿病的细菌,阿尔廷迪斯说. “Taken together with our analysis of the available gut microbiota data from children developing type 1 diabetes, we are one step closer to understanding the potential link between gut microbiome—in particular the microbe Parabacteriodes distasonis还有这种复杂的自身免疫性疾病.”
根据青少年糖尿病电子游戏正规平台基金会(JDRF)，有1.6 million Americans living with this chronic disease and this number is expected to increase to 5 million by 2050.
“尽管我们已经知道1型糖尿病几千年了, 原因尚不清楚,阿尔廷迪斯说, 他的电子游戏正规平台得到了美国国立卫生电子游戏正规平台院的支持, G. 哈罗德和蕾拉. 马瑟斯慈善基金会和JDRF. “While genetics studies have identified mutations in some human genes that increase the risk of developing type 1 diabetes, genetics alone cannot fully explain the increasing incidence rates in the world, 特别是在工业化国家.”
A central question for researchers is what turns the body’s immune system against itself.
"The primary role of 免疫系统 is to recognize self and non-self and protect the body from the non-self,阿尔廷迪斯说. “当这个识别系统受损时, our immune cells start to attack not only foreign cells but also our own cells. 这种受损的免疫系统机制导致自身免疫性疾病.”
Recent type 1 diabetes gut microbiome studies observed that the composition of the gut microbiome in type 1 diabetes patients was significantly different from individuals who do not have the disease.
然而, those studies did not establish a causal relationship between the microbiome and type 1 diabetes. “在这项电子游戏正规平台中, we identified a gut bacterium that is potentially linked to the disease onset,阿尔廷迪斯说.
当免疫系统检测到外来颗粒时, 它开始产生一种叫做抗体的蛋白质来摧毁它. 自身免疫性疾病, autoantibodies and immune cells target human proteins and insulin is the main target of 免疫系统 in type 1 diabetes. Altindis和他的同事们专注于分子模拟, a mechanism of autoimmune disease in which a foreign antigen that shares a structural similarity with a host protein can modify disease pathogenesis.
“基于胰岛素在1型糖尿病自身免疫中的核心作用, we hypothesized that type 1 diabetes is caused by a molecular mimicry mechanism in which exposure to a microbial insulin stimulates 免疫系统 against human insulin,阿尔廷迪斯说.
“还有更多的工作要做, 然而 this study and similar studies have the potential to guide us to develop new tools, 包括疫苗, 抗生素, 或益生菌, 用于预防和治疗1型糖尿病.”
以前, Altindis and his team made a surprising discovery and showed that viruses have insulin-like proteins. 在最新的项目中, 他们专注于胰岛素区域, 特别是肽, 或者一条氨基酸链——被称为胰岛素B链, or B:9-23—that is targeted by the immune cells in type 1 diabetes patients and identified mimics of this region in different microbes.The team hypothesized that because human insulin B:9-23 and microbialinsulin B:9-23 will be very similar, immune cells cannot distinguish the difference and an immune response to this bacterial B:9-23-like peptide will cross-react with the insulin and consequently will target and destroy the cells that produce insulin.
基于分子模仿假说, 电子游戏正规平台小组确定了17种与胰岛素b9 -23非常相似的微生物肽. 在1型糖尿病患者的免疫细胞中进行测试, 他们发现了一种细菌胰岛素B:9-23模拟肽 Parabacteriodes distasonis 可以刺激胰岛素的免疫细胞. 使用1型糖尿病的细胞和动物模型, Altindis and his colleagues showed that molecular mimicry might be triggering type 1 diabetes.
肠道菌群的定植 Parabacteriodes distasonis increased type 1 diabetes rates by increasing the inflammation in different tissues, 特别是胰腺, 用于1型糖尿病T1D电子游戏正规平台的小鼠, 这个团队 报道 in the article "A Gut Microbial Peptide and Molecular Mimicry in the Pathogenesis of Type 1 Diabetes."
这种细菌最有可能存在于人类的肠道中, 然而, the study indicates that the timing of exposure is important for the development of type 1 diabetes. 然后，电子游戏正规平台小组重新分析了已发表的人类肠道微生物组数据, 来自Broad基金会的DIABIMMUNE项目, to show that children up to age three tend to develop type 1 diabetes if they are exposed to this peptide/bacterium in early life.
“Our findings analyzing published human type 1 diabetes microbiome dataobtained from 269 infants gut microbiome, 样本年龄从0岁到3岁, 支持我们的假设暴露在这种细菌下, 更具体地说是胰岛素B:9-23样细菌肽, 在生命的前三年是一个潜在的危险因素,阿尔廷迪斯说.
确定肽的存在是一个重要的步骤, 说Altindis, 谁和C合作过这个项目. 罗纳德·卡恩, MD, 乔斯林糖尿病中心的医生, researchers at the University of Florida and the Benaroya 电子游戏正规平台 Institute, 以及包括博士后电子游戏正规平台员Khyati Girdhar在内的BC团队, BC流式细胞术实验室主任Patrick Autissier说, 以及本科生克劳迪娅·布雷迪和阿莫尔·莱辛加尼.
但他补充说，还有很多工作要做.
“While in this study we showed that the human immune cells that were specific to human insulin B:9-23 were reacting to the P. distasonis 肽 P. distasonis 能在小鼠模型中促进1型糖尿病的发展吗, 我们必须证明这种增强与肽直接相关,阿尔廷迪斯说.
为了证明, Girdhar is making a mutation in the bacterial genome by deleting the mimic peptide and will test its effects on the animal model, Altindis说. The team will also analyze another, more comprehensive type1 diabetes study, known as TEDDY.
“如果这些电子游戏正规平台支持我们的发现, 这将支持我们最初的分子模拟机制,阿尔廷迪斯说. “还有更多的工作要做, 然而 this study and similar studies have the potential to guide us to develop new tools, 包括疫苗, 抗生素, 或益生菌, 用于预防和治疗1型糖尿病.”
艾德·海沃德|大学传播| 2022年9月