Impacts of Benzo[a]pyrene on Microbiome Development across Lifespan and Generations and the Behavioral Consequences

项目摘要/摘要 该项目将测试这一创新假设，即发育过程中暴露于环境毒物可以 改变肠道微生物群的组装和演替，从而导致行为和认知受损。这个 行为和认知障碍的惊人增加与生命早期接触环境化学物质有关， 例如苯并[a]芘(BAP)，这是本项目重点关注的全球普遍存在的污染物。而当 这些损伤背后的机制仍然不清楚，以前的工作涉及到肠道功能失调。 微生物组。该项目将定义早年接触BAP如何改变肠道微生物群的发育 结构和功能，以及这些变化与行为的关系。它还将结合高通量培养 使用可扩展的无菌动物模型(斑马鱼)来全面衡量 对苯并苯敏感的肠道微生物及其代谢产物。该项目还量化了BAP如何发展 在接下来的几代人中，暴露改变了微生物组的行为轴。因此，拟议的 研究具有巨大的潜力，可以改变我们对行为障碍原因的理解，并揭示 以肠道微生物和代谢物的形式，为行为发育正常化提供新的候选者。

Project Summary / Abstract This project will test the innovative hypothesis that developmental exposure to environmental toxicants can alter gut microbiome assembly and succession to consequently result in impaired behavior and cognition. The alarming rise in behavioral and cognitive disorders is linked to early life exposure to environmental chemicals, such as benzo[a]pyrene (BAP), the globally ubiquitous pollutant on which this project focuses. While the mechanisms underlying these impairments remain poorly defined, prior work implicates a dysbiotic gut microbiome. This project will define how early life exposure to BAP alters the development of gut microbiome structure and function and how these alterations relate to behavior. It will also couple high-throughput culturing with a scalable, germ-free animal model (zebrafish) to comprehensively measure the behavioral impacts of BAP-sensitive gut microbes and their metabolites. This project also quantifies how developmental BAP exposure alters the microbiome-behavior axis in subsequent generations. Consequently, the proposed research holds great potential to transform our understanding of the causes of behavior impairment and reveal new candidates, in the forms of gut microbes and metabolites, for normalizing behavior development.