The impact of dietary proteins for mucosal homeostasis and inflammation

膳食蛋白质对粘膜稳态和炎症的影响

• 批准号: 316144147
• 负责人: Professorin Dr. Britta Siegmund
• 金额: --
• 依托单位: Biomedizinisches Forschungszentrum Marburg
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/316144147?language=en
• 关键词: impact; dietary; proteins; mucosal; homeostasis

Based on our preliminary findings, we hypothesize that dietary proteins are essential for the maintenance of a normal intestinal immune compartment and barrier function. Here, we aim to reveal the effects of dietary protein on intestinal barrier function and T cell activation in the healthy and inflamed gut. This will be addressed in three steps. A) Intestinal homeostasis by specific immune recognition of food proteins. We will study whether susceptibility to intestinal inflammation is linked with recognition of food protein by the adaptive immune system. Immunocompetent, Rag1 KO and IL-10-Foxp3 reporter mice fed conventional (Conv) or protein-free (FAF) diet will be analysed for immunological responses, colitis development and intestinal barrier function. B) Dietary protein affects membrane integrity via an altered microbiome and gene expression. We will dissect the impact of both components on colitis development and intestinal membrane integrity. The experimental approach includes faecal transplantation and/or administration of protein in the presence or absence of microflora. These experiments will provide important information about the effects of a diet-altered microbiome and changes in intestinal gene expression for increased susceptibility to colitis. C) Nutritional therapies in Crohns disease (CD) patients. To translate the murine findings to human disease, we will study whether T cell hyperactivation observed in CD patients can be controlled by nutrional therapy. Intestinal T cells from patients and controls will be analyzed before and after nutritional therapy (elemental or parenteral diet). Further, T cell activation in the peripheral blood will be compared between patients. The data will provide insight how dietary protein regulates mucosal and peripheral T cell activation influencing the intestinal barrier function.

根据我们的初步研究结果，我们假设膳食蛋白质对维持正常的肠道免疫区室和屏障功能至关重要。在这里，我们的目标是揭示膳食蛋白质对健康和炎症肠道中肠道屏障功能和T细胞活化的影响。这将分三个步骤解决。A）通过食物蛋白质的特异性免疫识别的肠内稳态。我们将研究肠道炎症的易感性是否与适应性免疫系统对食物蛋白质的识别有关。将分析饲喂常规（Conv）或无蛋白（FAF）饲料的免疫活性、Rag 1 KO和IL-10-Foxp 3报告基因小鼠的免疫应答、结肠炎发展和肠屏障功能。B）膳食蛋白质通过改变的微生物组和基因表达影响膜完整性。我们将剖析这两种成分对结肠炎发展和肠膜完整性的影响。实验方法包括粪便移植和/或在存在或不存在微生物的情况下给予蛋白质。这些实验将提供有关饮食改变的微生物组和肠道基因表达变化对结肠炎易感性增加的影响的重要信息。C）克罗恩病（CD）患者的营养疗法。为了将小鼠的发现转化为人类疾病，我们将研究在CD患者中观察到的T细胞过度活化是否可以通过营养治疗来控制。将在营养治疗（元素或胃肠外饮食）前后分析患者和对照组的肠道T细胞。此外，将在患者之间比较外周血中的T细胞活化。这些数据将提供膳食蛋白质如何调节影响肠屏障功能的粘膜和外周T细胞活化的见解。