Chylomicron-responsive Tregs in EED

EED 中的乳糜微粒反应性 Tregs

基本信息

批准号：
10511826
负责人：
Timothy Wesley Hand
金额：
$ 23.82万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-08 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10511826
关键词：
Address Anti-Inflammatory Agents Antibiotics Biological Markers Blood Circulation Body Weight Bypass Calories Carbohydrates Characteristics Child Chronic Chylomicrons Clinical Cognitive Colon Coupled Diet Dietary Fats Dietary Intervention Disease Enteral Etiology Exhibits FOXP3 gene Fat-Restricted Diet Fatty acid glycerol esters Fistula Focus Groups Foundations Functional disorder Genus Hippocampus Goals Gold Growth Hand Human Inflammation Inflammatory Interleukin-10 Intestinal Absorption Intestinal Diseases Intestines Lipids Low Density Lipoprotein Receptor Lymph Malabsorption Syndromes Malnutrition Measures Medium chain triglycerides Mesentery Metabolic Metabolism Micronutrients Modeling Mus Nutritional Nutritional Support Pathology Pathway interactions Patients Pattern Pharmaceutical Preparations Plasma Politics Regulatory T-Lymphocyte Role Signal Transduction Small Intestines Source Testing Therapeutic Travel Triglycerides Tumor-infiltrating immune cells UNICEF Villus Weight absorption dietary drinking water dysbiosis experience global health in vivo lipid metabolism low income country microbiota mortality mouse model negative affect novel nutrient absorption reconstitution response restoration transcription factor transcriptome treatment strategy

项目摘要

Abstract. A quarter of the world’s children experience chronic malnutrition coupled with a lack of access to clean drinking water. This combination results in Environmental Enteric Dysfunction (EED), a disease where intestinal malabsorption exacerbates malnutrition, leading to increased cognitive deficiencies, stunted growth and mortality. The intestine of EED patients is characterized by inflammation and flattened villi in the small intestine that negatively affect absorptive capacity. Our groups have recently identified a pool of protective Tregs in the small intestine that respond specifically to dietary lipid absorption, to the presence or absence of chylomicrons secreted in response to dietary lipids, and to EED. We hypothesize that lipid absorption and chylomicron secretion is reduced in the EED intestine, that EED-chylomicrons deliver less dietary triglyceride to mesenteric LN Tregs, and that replenishing calories by bypassing the chylomicron pathway (with a medium-chain- triglycerides) will restore calories without blocking the effect EED-chylomicrons that will travel by the lymph to stimulate protective intestinal Tregs.

抽象的。世界上四分之一的儿童患有慢性营养不良，并且无法获得清洁饮用水这种组合会导致环境肠道功能障碍（EED），这是一种肠道疾病。吸收不良会加剧营养不良，导致认知缺陷加剧、生长发育迟缓和 EED 患者的肠道特点是小肠炎症和绒毛扁平。我们的团队最近在大脑中发现了一组具有保护作用的 Tregs。小肠对饮食中的脂质吸收、乳糜微粒的存在或不存在有特异性反应我们追求的是脂质吸收和乳糜微粒。 EED 肠道分泌减少，EED 乳糜微粒向肠系膜输送的膳食甘油三酯减少 LN Tregs，通过绕过乳糜微粒途径（具有中链- 甘油三酯）将恢复热量，而不会阻碍 EED 乳糜微粒的作用，乳糜微粒将通过淋巴液传播至刺激保护性肠道 Tregs。