Chylomicron-responsive Tregs in EED

EED 中的乳糜微粒反应性 Tregs

• 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
• 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

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。 世界上有四分之一的儿童长期营养不良，而且无法获得清洁饮用水。 水这种组合导致环境性肠功能障碍（EED），一种肠道疾病， 吸收不良加剧营养不良，导致认知缺陷增加，生长发育迟缓， mortality. EED患者的肠道特征是小肠中的炎症和扁平绒毛 这对吸收能力产生了负面影响。我们的研究小组最近发现， 小肠对膳食脂质吸收、乳糜微粒的存在或不存在有特异性反应 对饮食脂质和EED的反应。我们假设脂质吸收和乳糜微粒 EED肠道中的分泌减少，EED-乳糜微粒向肠系膜递送较少的膳食甘油三酯 LN Tlymphocyte，以及通过绕过乳糜微粒途径（具有中链- 甘油三酯）将恢复热量，而不会阻止EED-乳糜微粒的作用，这些乳糜微粒将通过淋巴， 刺激保护性肠肌张力。