Engineered Nanomaterial Synthesis, Characterization and Method Development Center for Nano-safety Research

拟议的补充项目是哈佛和PNNL之间的合作努力， 行政补充通知#NOT-ES-19 - 013。由于其高表面积和多种化学性质， 二维纳米材料（2DNM）具有许多潜在的重要社会应用，包括在 食品工业、药物输送、成像和生物传感以及农业实践。然而， 人类接触这些新材料可能产生的健康危害知之甚少， 所有的胃肠道。2DNM对肠上皮的损伤可引起局部和全身病理学， 以及对液体、营养物和毒素的消化和吸收的干扰。口服暴露于2DNM可能 改变肠道微生物组的代谢活动和群落组成，这反过来可能影响 人体健康我们对新兴2D ENM对胃肠道终点的影响缺乏了解， 重要的知识差距。这项合作努力的目标是开发、验证和采用体外 能够系统研究摄入的2DNM对肠道上皮的影响的方法 和微生物组在NHIR内部初步研究的基础上，哈佛和PNNL将合作使用 体外胃肠道消化系统，结合口-胃-小肠三相模拟消化 系统和结肠微生物组反应器，以通过3个目标解决这一知识差距：1）表征 摄入的2DNM与食物基质的相互作用，它们在GIT中的物理化学转化， 对小肠上皮的潜在影响; 2）表征摄入的2DNM对肠道的影响 微生物种群;和3）表征摄入的2DNM对肠道代谢组的影响。的 拟议的补充研究将提供必要的资源，以扩大国家健康影响研究联盟，包括 与纳米材料口服接触途径相关的微生物组成分。我们期待着 这项跨学科的工作将为一种新的体外系统提供基础， 纳米材料危害分析，并可在今后的工作中扩展到其他类型的颗粒物， 环境化学品暴露对NIEHS任务的重要性。

The proposed supplement project is a collaborative effort between Harvard and PNNL in response to the administrative supplement notice# NOT-ES-19-013. Due to their high surface area and diverse chemical functionality, 2D nanomaterials (2DNMs) have many potential important societal applications, including in the food industry, drug delivery, imaging and biosensing, and in agriculture practices. However, the potential health hazards of these emerging materials that may arise due to human exposure is poorly understood, least of all in the GI tract. Damage by 2DNMs to intestinal epithelium could cause local and systemic pathology, as well as disturbances in digestion and absorption of fluids, nutrients and toxins. Oral exposure to 2DNMs could alter the metabolic activities and community compositions of the gut microbiome, which in turn may impact human health. Our lack of understanding of the effects of emerging 2D ENMs on GI tract endpoints is an important knowledge gap. The objective of this collaborative effort is to develop, validate and employ an in vitro methodology that enables the systematic investigation of the effects of ingested 2DNMs on the gut epithelium and microbiome. Building on preliminary studies within the NHIR, Harvard and PNNL will collaborate to use an in vitro GI tract digestion system, combining a three-phase oral-gastric-small intestinal simulated digestion system, and a colonic microbiome reactor to address this knowledge gap through 3 aims: 1) characterize the interactions of ingested 2DNMs with food matrix, their physicochemical transformations across the GIT and potential effects on the small intestinal epithelium; 2) characterize the effects of ingested 2DNMs on the gut microbial populations; and 3) characterize the effects of ingested 2DNMs on the gut metabolome. The proposed supplement studies will provide the resources necessary to extend the NHIR consortium to include microbiome components associated with oral exposure routes for nanomaterials. We expect the success of this interdisciplinary work will provide the foundation for a novel new in vitro system useful for rapid nanomaterial hazard analyses, and which could be extended in future work to other types of particulates and environmental chemical exposures of importance to NIEHS missions.