Effects of ingestion of manufactured nanoparticles on endogenous microbiota and pathogen resistance in rainbow trout

PI：Henry，Theodore B.提案编号：1435874机构：田纳西大学农业研究所标题：摄取制造的纳米颗粒对虹鱼内源微生物区系和病原菌抗性的影响本提案的目的是了解纳米颗粒(NP)在肠道微生物群落中诱导的变化和对宿主反应的影响。总体假设是，摄入纳米材料，特别是那些具有抗微生物特性的材料，将改变鲑鱼的微生物群(共享身体空间的微生物群落)，导致不利的健康后果。研究人员计划调查NP挑战导致的微生物组的变化，假设这些变化将导致免疫抑制和增加病原体感染的机会。这一假设将通过细菌病原体挑战来检验。这项研究的结果将为NPs对肠道微生物群的影响提供新的见解，这不仅与鲑鱼有关，而且对人类和其他生物也有意义，因为这些基本的宿主-微生物群相互作用在所有脊椎动物中都是保守的。从拟议的调查中获得的数据也可能对行业和监管机构都有所帮助，因为行业正在制定毒性较低的新NPs，或者监管机构希望减少人类和野生动物对NPs的暴露。该提案包括对研究生和本科生进行出色的推广和培训，以及让高中生参与研究。这一研究结果可能会指导监管机构。所使用的模型将是与环境相关且具有商业意义的彩虹鲑鱼，Oncorhynchus mykiss。研究人员将使用高通量测序来了解微生物组的变化，具体地说，饮食暴露于NPs的影响将通过微生物群落的全球基因组测序和针对特定微生物物种的定量PCR来确定。特定微生物丰度的变化将在不同的治疗方法之间和随着时间的推移进行评估。在同一种鱼中，将进行基因表达谱分析，以确定对微生物群落组成变化做出反应的生物标记基因。将选择NP治疗的一个子集，对随后将暴露于伊氏杆菌的鱼类进行较长期的暴露，并将评估这一细菌挑战的结果。

PI: Henry, Theodore B. Proposal Number: 1435874Institution: University of Tennessee Institute of Agriculture Title: Effects of ingestion of manufactured nanoparticles on endogenous microbiota and pathogen resistance in rainbow troutThe objective of this proposal is to understand changes induced in the gut microbial community and on the host responses by nanoparticles (NPs). The overall hypothesis is that ingestion of nanomaterials, especially those that have anti-microbial properties, will change the microbiome (the community of microorganisms that share the body space) of trout resulting in adverse health outcomes. The investigators plan to investigate the changes in the microbiome resulting from the NP challenges, hypothesizing that these changes would lead to immunosuppression and increased opportunity for pathogen infection. The hypothesis will be tested with a bacterial pathogen challenge. The results of this investigation will provide new insights into the impact of NPs on the gut microbiome, which will have relevance not just for trout, but for humans and other organisms as well, since these fundamental host-microbiome interactions are conserved across all vertebrates. The data obtained from the proposed investigations can also be helpful for both industry and regulators as industry formulates new NPs with lower toxicity or regulators look to reduce exposure of humans and wildlife to NPs. The proposal includes excellent outreach and training of graduate and undergraduate students, as well as the involvement of high school students, in research. The research results can potentially guide regulatory agencies.The model used will be the environmentally relevant and commercially significant rainbow trout, Oncorhynchus mykiss. The investigators will use high throughput sequencing to understand the changes in the microbiome, specifically, the effects of dietary exposure to NPs will be determined by global genomic sequencing of the microbial communities and quantitative PCR to target specific microbial species. Changes in abundance of the specific microbes will be evaluated among treatments and over time. In the same fish, gene expression profiling will be conducted to identify biomarker genes that respond to alterations in the microbial community composition. A subset of NP treatments will be selected to conduct longer-term exposure in fish that will subsequently be exposed to Y. ruckeri and the outcome of this bacterial challenge will be evaluated.