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。这个 这项应用的目标是研究MP如何诱导肠上皮细胞和 巨噬细胞，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。我们的初步数据挑战了世卫组织目前的立场 这不可能就MP对人类的毒性得出任何确定的结论。为了挑战这一说法，我们将 利用人类肠道类器官、原代人类巨噬细胞和动物模型来了解 摄取MP的后果。基于我们的初步研究，我们提出了一个新的假设，即MP 摄入确实对人类健康构成危害，因为它扰乱了上皮细胞和 巨噬细胞随后导致肠道通透性、生物失调和免疫代谢活跃状态 这可能会导致肠道炎症。此外，我们假设摄入MP会对健康产生重大影响。 对有潜在疾病的个人的风险，如IBD患者的肠道炎症。在……里面 目的1，我们将建立MP如何通过细胞代谢改变促进肠道通透性。 上皮细胞和肠道代谢体。在目标2中，我们将确定MP对易感人群胃肠道的影响。 主持人。目的3阐明MP对人巨噬细胞代谢的调控机制及其影响 对肠道屏障的影响。这个项目产生的信息将是具有开创性的一步 了解MP如何通过以下途径影响肠道稳态的重要长期意义 上皮细胞和巨噬细胞功能的调节与整体人类健康。 项目摘要页面

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. The goals of this application are to investigate how MP induce cellular changes in both intestinal epithelial cells and macrophages and to determine how these MP-induced changes in cellular pathways can lead to intestinal permeability, dysbiosis and an inflammatory state. Our preliminary data challenges the current stance of WHO that is not possible to draw any firm conclusions on MP toxicity to humans. To challenge this statement, we will utilize human intestinal organoids, primary human macrophages and animal models to understand the consequence of MP ingestion. Based on our preliminary studies, we advance a novel hypothesis that MP ingestion indeed pose a human health hazard by disrupting oxidative metabolism in both epithelial cells and macrophages 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. In aim 1, we will establish how MP contribute to intestinal permeability through cellular metabolic changes in the epithelium and gut metabolome. In Aim 2, we will determine the effects of MP on the GI tract of a susceptible host. Aim 3 will delineate the mechanism of MP modulation of human macrophage metabolism and its impact on the intestinal barrier. 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 and macrophage function and overall human health. Project Summary Page