Defining the Harmful Effects of Microplastics on Gastrointestinal Health

定义微塑料对胃肠道健康的有害影响

• 批准号: 10367419
• 负责人: Eliseo F Castillo
• 金额: $ 38.32万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-22 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10367419
• 关键词: Adherent Culture; Affect; Anaerobic Bacteria; Applications Grants; Awareness; Cell Line; Cell Respiration; Chronic; Data; Dose; Environmental Health; Epithelial; Epithelial Cells; Exposure to; Face; Food; Functional disorder; Gastrointestinal tract structure; General Population; Glycolysis; Goals; Health; Health Hazards; Human; Immune system; Individual; Inflammatory; Inflammatory Bowel Diseases; Ingestion; Intestinal permeability; Intestines; Knowledge; Lead; Maintenance; Metabolic; Metabolism; Mitochondria; Modeling; Mus; Organ; Organoids; Oxygen; Oxygen Consumption; Pathology; Pathway interactions; Patients; Persons; Pollution; Population; Principal Investigator; Proteins; Public Health; Research; Risk; Source; System; Testing; Tight Junctions; UV Radiation Exposure; Water; Zebrafish; base; combat; dysbiosis; gastrointestinal; gut dysbiosis; gut inflammation; gut microbiota; health knowledge; in vivo; insight; intestinal epithelium; intestinal homeostasis; metabolome; microbial; mitochondrial metabolism; monolayer; novel; particle; particle exposure; preservation; prevent; programs; systemic inflammatory response

Program Director/Principal Investigator: Castillo, Eliseo, F PROJECT SUMMARY Plastic pollution and the breakdown of plastic materials primarily into micron-sized microplastic particles (MP) have contaminated our food and water sources, raising public health concerns. MP ingestion by humans is now an inevitable consequence of global plastic pollution and there is a critical gap in knowledge as to how MP impact human health (WHO). There is also an important gap in knowledge regarding how MP affect the major direct organ of contact, the gastrointestinal (GI) tract. The studies proposed in this grant application seek to bridge this gap in environmental health knowledge and provide insight into how MP pose a significant health risk to the general population as well as susceptible (i.e. Inflammatory Bowel Disease; IBD) individuals. Our preliminary data provides evidence chronic MP exposure affects the GI tract specifically causing gut dysbiosis, low-level intestinal inflammation, and alterations in cellular metabolism. Based on our preliminary studies, we advance a novel hypothesis that MP ingestion indeed pose a human health hazard by disrupting oxidative metabolism in epithelial cells subsequently causing intestinal permeability, dysbiosis, and an immunometabolic active state which could lead to intestinal inflammation. Additionally, we hypothesize MP ingestion pose a significant health risk to individuals that have an underlying condition such as intestinal inflammation as seen in IBD patients. The goals of this application are to investigate how MP induce cellular changes in intestinal epithelial cells and to determine how these MP-induced changes in cellular pathways can lead to intestinal permeability, dysbiosis and an inflammatory state. In aim 1, we will investigate the effects of varying doses and types of MP on intestinal permeability in a zebrafish model. In Aim 2, we will determine the mechanism behind MP induced dysbiosis and intestinal permeability. Aim 3 will delineate how an intact human intestinal tract responds to microplastics through the use of human colonoids derived from health patients as well as IBD patients. The information generated from this project would be a ground-breaking step with important long-term implications in understanding how MP can affect intestinal homeostasis through modulation of epithelial barrier function and overall human health.

项目主任/主要研究者：Castillo，Eliseo，F 项目摘要 塑料污染和塑料材料主要分解成微米级的塑料微粒（MP） 污染了我们的食物和水源，引起了公众的健康关切。人类对MP的摄入量 现在是全球塑料污染的不可避免的后果，关于MP如何使用， 影响人类健康（卫生组织）。关于MP如何影响专业， 直接接触器官，胃肠道（GI）。本补助金申请中提出的研究旨在 弥合环境健康知识的这一差距，并深入了解MP如何对健康构成重大影响。 对一般人群以及易感（即炎症性肠道疾病; IBD）个体存在风险。我们 初步数据提供了证据表明慢性MP暴露影响胃肠道，特别是引起肠道生态失调， 低水平的肠道炎症和细胞代谢的改变。根据我们的初步研究， 提出了一个新的假设，即MP摄入确实通过破坏氧化， 上皮细胞的代谢随后引起肠通透性、生态失调和免疫代谢紊乱。 活跃状态，可能导致肠道炎症。此外，我们假设MP摄入造成 对患有潜在疾病（如肠道炎症）的个体有重大健康风险， IBD患者本申请的目的是研究MP如何诱导肠道细胞的变化， 上皮细胞，并确定这些MP诱导的细胞通路的变化如何导致肠上皮细胞 渗透性、生态失调和炎症状态。在目标1中，我们将研究不同剂量的影响， MP类型对斑马鱼模型肠通透性的影响。在目标2中，我们将确定 MP诱导的生态失调和肠通透性。目标3将描述一个完整的人体肠道 通过使用来自健康患者以及IBD的人类结肠对微塑料做出反应 患者该项目产生的信息将是具有重要长期意义的突破性步骤 了解MP如何通过调节上皮屏障影响肠内稳态的意义 功能和整体人类健康。