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

项目概要 该项目专门针对海洋和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 (COHH3) (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 与气候变化相关的健康影响的毒性机制； (3) 针对美国人口 沿海和五大湖地区（例如，那些存在健康或社会差距的地区）将更多 容易受到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。此举的目标 该项目旨在了解和量化接触弧菌物种（创伤弧菌和弧菌）的影响。 副溶血性杆菌）和蓝藻（如铜绿微囊藻）毒素产生增加。的 气候变化的影响可能会增加这些微生物的发生率，从而导致潜在的更大风险 通过食物链和其他接触途径接触。具体来说，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 单独和组合。此外，暴露还包括微塑料，这是环境的主要污染物。 随着城市化进程的加快，沿海和水生生态系统日益受到关注 随着人们感受到气候变化的影响，这种影响也在增加。这些成分的混合效果将 通过适当的实验设计和统计分析进行研究。对重要器官的影响 系统（肝、肾和肠道）、炎症改变和疾病状态增加（非酒精性肝病） 疾病包括人类非酒精性脂肪肝病（NAFLD）和非酒精性脂肪性肝炎（NASH）， 以及多囊卵巢综合症（PCOS）），将被量化。我们有初步数据显示 现有慢性非酒精性脂肪肝病的啮齿动物模型中微囊藻毒素的暴露会加剧 肝脏病理学导致肾脏和肝脏桥接纤维化。我们还发现了显着的变化 暴露于微囊藻毒素后的肠道微生物群导致肠道滤出和门静脉内毒素血症，这是 通过模式识别受体（TLR 和 P2X7rs）抑制全身炎症和器官损伤。此外， 微塑料可能含有多种内分泌干扰化学物质，最近发现微囊藻毒素 据报道表现出内分泌干扰作用，这两种作用都可能导致生殖功能障碍。 最后，将评估微塑料对海鲜安全的影响。微塑料的新兴作用及其 双壳类软体动物（牡蛎）、鱼类和其他海洋生物的消耗及其作为载体的能力 对于其他污染物，例如微囊藻毒素，对人类健康构成严重威胁，特别是 由于世界各地对这些食品的依赖日益增加。该项目显然支持双向对话 在社区参与核心内发起，同时与弧菌和 蓝藻项目生产具有更强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