Effects of selected climate change-affected pathogens and pollutants on Critical Organs, Inflammation and Human disease

项目摘要 该项目具体针对海洋中心范围的以下方面， 人类健康3：气候变化对海洋和五大湖的影响（COHH 3）（P01）：1）确定 气候变化对有害藻华（HAB）事件发生率增加的影响;（2）了解 与气候变化相关的潜在健康影响的毒性机制;（3）解决美国人口问题 沿海和五大湖地区（例如，那些存在健康或社会差距的人）， 易受与气候变化相关或因气候变化而加剧的人类健康风险的影响。这个目标 该项目的目的是了解和量化暴露弧菌物种（创伤弧菌和弧菌）的影响。 副溶血性弧菌）和增加的毒素产生的蓝细菌，如铜绿微囊藻。的 气候变化的影响可能会增加这些微生物的发病率， 通过食物链和其他接触途径接触。具体而言，该项目将评估 气候变化改变的弧菌和微囊藻毒素对哺乳动物模型暴露系统的影响 单独地和组合地。此外，暴露将包括微塑料，这是一种主要的污染物， 沿海和水生生态系统中新出现的问题，与城市化的增加有关， 随着气候变化的影响而增加。这些组分的混合物的效果将 通过适当的实验设计和统计分析进行研究。对关键器官的影响 系统（肝脏，肾脏和肠道），炎症改变和疾病状态增加（非酒精性肝脏） 疾病，包括人非酒精性脂肪性肝病（NAFLD）和非酒精性脂肪性肝炎（NASH）， 沿着多囊卵巢综合征（PCOS））。我们有初步数据显示 在现有慢性非酒精性脂肪性肝病啮齿动物模型中暴露微囊藻毒素会加剧 导致肾脏和肝脏桥接纤维化的肝脏病理学。我们还发现， 微囊藻毒素暴露后的肠道微生物组，导致肠道浸出和门静脉内毒素血症， 通过模式识别受体（TLR和P2 X7 rs）的全身性炎症和器官损伤。此外，本发明还提供了一种方法， 微塑料可能含有多种内分泌干扰化学物质，微囊藻毒素最近被 据报告，这两种物质都表现出内分泌干扰作用，可能导致生殖功能障碍。 最后，将评估微塑料对海产品安全的影响。微塑料的新兴作用， 双壳类软体动物（牡蛎）、鱼类和其他海洋生物的食用量及其作为病媒的能力 对于其他污染物，如微囊藻毒素，对人体健康构成严重威胁，特别是 因为全世界对这些食物的依赖越来越大。该项目显然支持双向对话 在社区参与核心中受到煽动，同时也与弧菌有明显的联系， 蓝细菌项目生产具有更高毒性测试效力的细菌和毒素。 1

PROJECT SUMMARY This project is specifically responsive to the following aspects of the scope of the Centers for Oceans and Human Health 3: Impacts of Climate Change on Oceans and Great Lakes (COHH3) (P01): 1) determine impacts of climate change on increasing incidence of harmful algal bloom (HAB) events; (2) understand mechanisms of toxicity underlying health impacts linked to climate change; (3) address populations in US coastal and Great Lakes regions (e.g., those with existing health or social disparities) that will be more vulnerable to human health risks that are associated with or exacerbated by climate change. The goal of this project is to understand and quantify the impacts of exposure Vibrio species (V. vulnificus and V. parahaemolyticus) and increased toxin production in Cyanobacteria such as Microcystis aeruginosa. The effects of climate change are likely to increase the incidence of these microbes leading to potentially greater exposure through the food chain and via other exposure routes. Specifically, this Project will assess the effects of climate change-altered Vibrio bacteria and Microcystin toxin on mammalian model exposure systems individually and in combination. In addition, exposures will include microplastics, a major contaminant of emerging concern in coastal and aquatic ecosystems, correlated with increased urbanization, which is increasing as the effects of climate change are being felt. The effects of the mixture of these components will be investigated through appropriate experimental design and statistical analysis. Effects on critical organ systems (liver, kidney and gut), alterations in inflammation and increased disease states (non-alcoholic liver disease including human non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), along with and polycystic ovarian syndrome (PCOS)), will be quantified. We have preliminary data that shows the exposure of microcystins in rodent models of existing chronic nonalcoholic fatty liver disease exacerbate liver pathology leading to bridging fibrosis in both kidney and livers. We also found significant alterations in the gut microbiome following microcystin exposure that led to gut leaching and portal endotoxemia, a recipe for systemic inflammation and organ damage via pattern recognition receptors (TLRs and P2X7rs). In addition, microplastics can contain multiple endocrine disrupting chemicals and microcystins have recently been reported to exhibit endocrine disrupting effects, both of which potentially lead to reproductive dysfunctions. Lastly, effects of microplastics on seafood safety will be evaluated. The emerging role of microplastics, their consumption by bivalve molluscs (oysters), fish and other marine organisms and theuir ability to act as vectors for other pollutants such as the microcystin toxins, pose a serious threat to the human health, in particular owing to increasing reliance on these foods around the world. This Project clearly underpins two-way dialogue instigated within the Community Engagement Core, while there are also clear links with the Vibrio and Cyanobacteria Projects to produce bacteria and toxins with greater potency for toxicity testing. 1