Diet and microbiota in type 1 diabetes

1 型糖尿病的饮食和微生物群

• 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
• 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

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）：在许多受共生菌群影响的人类疾病中，这两种类型都是糖尿病-Type 1（T1D），由于胰岛素产生细胞的损失而出现，并且由于胰岛素诱导的组织中胰岛素诱导的信号的减弱而发展。对环境对T1D发病率的影响的研究引起了饮食改变疾病发病率的可能性。但是，对我们而言，很明显，消耗的营养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。微生物群的变化会改变影响宿主的代谢景观。为了在各种人群中使用保护性饮食，这些人群可能在微生物群中有显着差异，应该考虑找到与微生物群无关的最佳饮食。我们已经确定，含有水解酪蛋白（HC）作为蛋白质来源的饮食在糖尿病易于的点头小鼠中具有保护性，而与微生物群的存在无关。此外，在HC饮食中添加面筋恢复了T1D的发展，但这种恢复取决于肠道菌群。最后，HC饮食并没有直接影响免疫系统，而是增强了产生胰岛素的细胞的活力。为了进一步揭示HC饮食保护性的机制，我们将追求以下目标。 1。调查饮食干预的极限，我们将研究暴露于HC饮食的时间，以引起其保护作用；我们将测试HC饮食通过糖尿病发作T细胞受体的转基因表达增强型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。研究小鼠中产生胰岛素细胞在不同饮食中的特性，我们将测试小鼠β细胞的功能 在不同的饮食上揭示压力的迹象；我们将在常规和HC饮食中测量小鼠的胰岛素抵抗。面筋对β细胞应激的贡献将得到研究。 3。研究与面筋的促糖尿病作用的微生物连接。我们将研究通过在HC饮食中添加面筋引起的微生物群的变化；我们将研究微生物群在 组织转谷氨酰胺酶表达的调节。