Diet and microbiota in type 1 diabetes

1 型糖尿病的饮食和微生物群

基本信息

批准号：
8815476
负责人：
ALEXANDER V CHERVONSKY
金额：
$ 19.75万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-12-01 至 2016-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8815476
关键词：
Affect Animals Autoimmunity Bacteria Beta Cell Caseins Cells Cellular Stress Development Diabetes Mellitus Diet Diet Modification Dietary Intervention Disease Exposure to Gene Expression Germ-Free Gluten Gnotobiotic Health High-Throughput Nucleotide Sequencing Human Immune system Inbred NOD Mice Incidence Insulin Insulin Resistance Insulin-Dependent Diabetes Mellitus Knowledge Link Measures Metabolic Methods Microbe Modeling Mus Non-Insulin-Dependent Diabetes Mellitus Nutrient Obesity Organism Outcome Physiological Population Process Property Proteins Protozoa Regulation Role Signal Transduction Source Stress T-Cell Receptor Testing Time Tissues Transgenic Organisms Transglutaminases Uncertainty Variant Work attenuation cell type diabetic fungus gut microbiota microbial microbial community prevent protective effect public health relevance reconstitution research study restoration transglutaminase 2

项目摘要

DESCRIPTION (provided by applicant): Among many human maladies that are affected by commensal microbiota are both types of diabetes -Type 1 (T1D), which develops due to the loss of insulin producing cells, and Type 2 (T2D), which develops due to the attenuation of the insulin-induced signaling in the tissues. The studies of environmental influences on T1D incidence evoked the possibility of dietary modification of the disease incidence. However, it was obvious to us that consumed nutrients are substrates for commensal microbiota, and changes in the diet can rapidly change the microbiota. Changes in microbiota can change the metabolic landscape affecting the host. For using protective diet in diverse human populations, which can have significant variation in microbiota, one should consider finding optimal diet that would be independent of microbiota variation. We have established that diet containing hydrolyzed casein (HC) as the protein source was protective in diabetes-prone NOD mice independently of the presence of microbiota. Moreover, addition of gluten to HC diet restored T1D development, but this restoration was dependent on intestinal microbiota. Finally, HC diet did not directly affect the immune system, but enhanced the vigor of insulin-producing cells. To further uncover the mechanisms behind protective properties of the HC diet, we will pursue the following aims. 1. Investigate the limits of dietary intervention We will investigate the time limts of exposure to HC diet to elicit its protective effect; We will test the ability of HC diet to protct animals with diabetogenesis enhanced by transgenic expression of diabetogenic T cell receptors. We will also test the role of gluten in these models. 2. Investigate the properties of insulin-producing cells in mice on different diets We will test the functions of beta cells in mice on different diets to reveal the signs of stress; We will measure insulin resistance in mice on regular and HC diet. The contribution of gluten to beta cell stress will be investigated. 3. Investigate the microbial connection to gluten's pro-diabetic action. We will study the changes in microbiota induced by addition of gluten to HC diet; We will study a possible role of microbiota in regulation of tissue transglutaminase expression.

描述（由申请人提供）：在受共生微生物群影响的许多人类疾病中，有两种类型的糖尿病：1 型糖尿病 (T1D) 是由于胰岛素产生细胞的丧失而发生的，而 2 型糖尿病 (T2D) 则是由于胰岛素产生细胞的丧失而发生的。从而减弱组织中胰岛素诱导的信号传导。环境对 T1D 发病率影响的研究引发了通过饮食调整来降低疾病发病率的可能性。然而，我们很明显，消耗的营养物质是共生微生物群的底物，饮食的变化可以迅速改变微生物群。微生物群的变化可以改变影响宿主的代谢格局。为了在微生物群存在显着差异的不同人群中使用保护性饮食，人们应该考虑寻找独立于微生物群变化的最佳饮食。我们已经确定，含有水解酪蛋白 (HC) 作为蛋白质来源的饮食对易患糖尿病的 NOD 小鼠具有保护作用，与微生物群的存在无关。此外，在 HC 饮食中添加麸质可以恢复 T1D 的发展，但这种恢复依赖于肠道微生物群。最后，HC饮食并没有直接影响免疫系统，而是增强了胰岛素生成细胞的活力。为了进一步揭示 HC 饮食保护特性背后的机制，我们将追求以下目标。 1. 研究饮食干预的局限性我们将研究暴露于HC饮食的时间限制，以得出其保护作用；我们将测试 HC 饮食保护通过致糖尿病 T 细胞受体的转基因表达而增强的糖尿病发生的动物的能力。我们还将测试麸质在这些模型中的作用。 2. 研究不同饮食小鼠体内胰岛素生成细胞的特性我们将测试小鼠体内β细胞的功能通过不同的饮食来揭示压力的迹象；我们将测量常规饮食和高浓度饮食小鼠的胰岛素抵抗。将研究麸质对β细胞应激的贡献。 3. 研究微生物与麸质促糖尿病作用的关系。我们将研究HC饮食中添加麸质引起的微生物群变化；我们将研究微生物群的可能作用组织转谷氨酰胺酶表达的调节。