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.

项目摘要 /摘要 该项目将测试创新的假设，即发育性接触环境有毒物质可以 改变肠道微生物组的组装和继承，从而导致行为和认知受损。这 行为和认知障碍的令人震惊 例如Benzo [A] Pyrene（BAP），该项目关注的全球无处不在的污染物。而 这些障碍基础的机制仍然很差，先前的工作暗示了肠道疾病 微生物组。该项目将定义生命早期暴露于BAP如何改变肠道微生物组的发展 结构和功能以及这些改变与行为的关系。它也将融入高通量培养 采用可扩展的，无菌的动物模型（斑马鱼），以全面衡量 BAP敏感的肠道微生物及其代谢产物。该项目还量化了发展的方式 暴露在随后的几代中改变微生物组行为轴。因此，提议 研究具有改变我们对行为障碍原因的理解并揭示的巨大潜力 以肠道微生物和代谢产物形式的新候选者，以使行为发展标准化。