Defining the Harmful Effects of Microplastics on Gastrointestinal 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（即炎症性肠病; IBD）个体的风险。的 本申请的目的是研究MP如何诱导肠上皮细胞和 巨噬细胞，并确定这些MP诱导的细胞途径的变化如何导致肠 渗透性、生态失调和炎症状态。我们的初步数据对世卫组织目前的立场提出了挑战 这是不可能得出任何关于MP对人类毒性的确切结论。为了反驳这一说法，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 MP摄入的后果。基于我们的初步研究，我们提出了一个新的假设，MP 摄入确实通过破坏上皮细胞和上皮细胞中氧化代谢而对人类健康造成危害， 巨噬细胞随后引起肠通透性、生态失调和免疫代谢活性状态 可能会导致肠道炎症此外，我们假设MP摄入对健康有显著影响。 对患有基础疾病（如IBD患者中所见的肠道炎症）的个体的风险。在 目的1，我们将确定MP如何通过细胞代谢变化促进肠道通透性， 上皮和肠代谢组。在目标2中，我们将确定MP对易感者胃肠道的影响。 主持人目的3探讨MP对人巨噬细胞代谢的调节机制及其对巨噬细胞代谢的影响 对肠道屏障的影响该项目产生的信息将是一个突破性的步骤， 重要的长期影响，了解MP如何影响肠道内稳态， 调节上皮细胞和巨噬细胞的功能和整体人类健康。 项目摘要页

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