Defining the Harmful Effects of Microplastics on Gastrointestinal Health

项目主任/首席调查员：卡斯蒂略，Eliseo，F 项目总结 塑料污染和塑料材料主要分解成微米级的微塑料颗粒(MP) 污染了我们的食物和水源，引发了公众对健康的担忧。人类摄入MP是 现在是全球塑料污染的必然后果，关于MP如何 影响人类健康(世卫组织)。关于国会议员如何影响少校，也有一个重要的知识差距 直接接触器官，胃肠道(GI)。在这项拨款申请中提出的研究旨在 弥合环境健康知识的这一差距，并提供对MP如何构成重大健康的洞察 对普通人群以及易感人群(即炎症性肠病；IBD)的风险。我们的 初步数据提供证据表明，慢性MP暴露会影响胃肠道，特别是导致肠道生物失调。 低水平的肠道炎症和细胞代谢改变。根据我们的初步研究，我们 提出一种新的假设，即摄入MP确实通过破坏氧化对人类健康造成危害 上皮细胞的代谢随后导致肠道通透性、生物失调和免疫代谢 可能导致肠道炎症的活跃状态。此外，我们假设MP的摄入会导致 对有肠道炎症等潜在疾病的个人造成重大健康风险 IBD患者。该应用程序的目标是研究MP是如何引起肠道细胞变化的 并确定这些MP诱导的细胞通路的变化如何导致肠道 渗透性、生物失调和炎症状态。在目标1中，我们将调查不同剂量和 在斑马鱼模型中MP的种类对肠道通透性的影响。在目标2中，我们将确定背后的机制 MP可引起肠道通透性和微生物代谢紊乱。目标3将描绘一个完整的人类肠道如何 通过使用来自健康患者和IBD患者的人类结肠样物质对微塑料做出反应 病人。这个项目产生的信息将是具有重要长远意义的开创性的一步 MP如何通过调节上皮屏障影响肠道动态平衡 功能和整体人类健康。

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.