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

苯并[a]芘对整个生命周期和几代人微生物组发育的影响以及行为后果

• 批准号: 10549792
• 负责人: Thomas Jefferson Sharpton
• 金额: $ 40.29万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10549792
• 关键词: Acute; Affect; Animal Model; Animals; Behavior; Behavior Disorders; Behavioral; Benzo(a)pyrene; Brain; Cognition; Cognition Disorders; Collaborations; Communication; Data; Development; Disease; Environmental Pollutants; Exposure to; Future Generations; Generations; Germ-Free; Goals; Growth; Impaired cognition; Impairment; Investigation; Life; Link; Longevity; Measures; Mediation; Metabolism; Methods; Microbe; Modeling; Nervous System; Neurodegenerative Disorders; Neurodevelopmental Disorder; Outcome; Parents; Phenotype; Physiological; Research; Resources; Sample Size; Structure; Systems Biology; Technology; Testing; Therapeutic; Toxic Environmental Substances; Work; Zebrafish; behavior influence; behavior measurement; behavioral impairment; dysbiosis; early life exposure; environmental chemical; environmental chemical exposure; frontier; gut microbes; gut microbiome; innovation; insight; intergenerational; metabolomics; microbial; microbiome; microbiome alteration; microbiome research; microbiota; neurodevelopment; neurophysiology; pollutant; prevent; success; toxicant

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.

项目概要/摘要 该项目将测试一个创新假设，即发育过程中接触环境毒物会导致 改变肠道微生物组的组装和演替，从而导致行为和认知受损。这 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， 例如本项目重点关注的全球普遍存在的污染物苯并[a]芘 (BAP)。虽然 这些损伤背后的机制仍不清楚，之前的工作表明肠道菌群失调 微生物组。该项目将定义生命早期接触 BAP 如何改变肠道微生物组的发育 结构和功能以及这些改变如何与行为相关。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）来全面测量以下行为的影响 BAP 敏感肠道微生物及其代谢物。该项目还量化了 BAP 的发展 暴露会改变后代的微生物组行为轴。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 肠道微生物和代谢物形式的新候选者可以使行为发展正常化。