Role of the gut microbiome in pesticide-induced effects on child neurodevelopment

肠道微生物群在农药对儿童神经发育的影响中的作用

• 批准号: 10540404
• 负责人: Antoine M Snijders
• 金额: $ 28.32万
• 依托单位: UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-17 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10540404
• 关键词: 16S ribosomal RNA sequencing; 4 year old; Affect; Anxiety; Artificial Intelligence; Atrazine; Bacteria; Behavior; Behavioral; Bioinformatics; Biological; Birth; Brain; C57BL/6 Mouse; Chemical Exposure; Chemicals; Child; Child Development; Child Health; China; Chinese; Chlorpyrifos; Data; Data Analyses; Data Collection; Degradation Pathway; Development; Developmental Delay Disorders; Diet; Dose; Environment; Environmental Exposure; Environmental Risk Factor; Etiology; Exposure to; Failure; Family health status; Food Supply; Germ-Free; Gnotobiotic; Growth; Health; Health Personnel; Herbicides; Human; Immunologic Deficiency Syndromes; Individual; Industrialization; Insecticides; Intervention; Lead; Life; Link; Manuscripts; Measures; Mediating; Medical; Memory; Moods; Mothers; Motor; Mus; Organ; Outcome; Paraquat; Participant; Pathway interactions; Pentachlorophenol; Performance; Persons; Pesticides; Phenotype; Phorate; Physiology; Play; Poison; Predisposition; Pregnancy; Pregnant Women; Prevention strategy; Probiotics; Public Health; Risk; Risk Assessment; Role; Sampling; Second Pregnancy Trimester; Serum; Social Interaction; Structure; Taxonomy; Testing; Toxic effect; United States; Universities; Validation; Water Supply; acaricide; biological systems; body system; brain tissue; carcinogenesis; cognitive performance; cohort; design; drinking water; experimental study; follow-up; glyphosate; gut bacteria; gut microbiome; gut microbiota; high risk; improved; individual variation; individualized prevention; microbial; microbial community; microbial composition; microbiome; microbiome analysis; microbiome components; microbiome composition; microbiome sequencing; motor behavior; mouse model; neurodevelopment; novel; offspring; pesticide exposure; pregnant; prenatal; prenatal environmental exposure; prenatal exposure; recruit; response; risk prediction model; sample collection; transcriptome sequencing

SUMMARY Pesticides are pervasive in our environment, and have accumulated in drinking water reserves serving millions of people worldwide, causing growing concern since the potential adverse health effects are not fully understood. In 2017 alone, the world used about 6.8 million tons of pesticides, of which the world's largest usage is in China and the United States. More recently it has been discovered that pesticides have strong effects on microbial communities, extinguishing entire clades while promoting growth in others. Shifts in microbial composition have been associated with brain development, mood and behavior suggesting a strong link between the gut and the brain. We hypothesize that there may exist an unappreciated microbiome component to the adverse health effects of pesticide exposure. In this proposal, we will use a comprehensive approach to identify the microbial components of pesticide susceptibility to neurodevelopmental delay. Specifically, in Aim 1 we will investigate the impact of prenatal exposure to 11 targeted pesticides on child neurodevelopment in a large well-defined human Mother and Child Microbiome Cohort (MCMC) consisting of 3000 mother and child pairs. Study participants are currently followed up regularly until the children reach 4 years of age. Comprehensive artificial intelligence analysis of pesticide exposure and children's early neurodevelopment data will identify key pesticides that negatively impact child development. In Aim 2, we hypothesize that prenatal exposure to pesticides can shift the composition of the GM and subsequently lead to abnormal neurodevelopment. We will integrate the child gut microbiome data with maternal pesticide exposure during pregnancy and child neurodevelopment data to investigate the impact of prenatal exposure to targeted pesticides on child gut microbiome and development. This Aim will identify specific gut bacteria or clades associated with child neurodevelopment. In Aim 3, we will use conventional and germ-free mouse models to elucidate mechanisms by which pesticide exposure can affect the gut microbiome and behavior. Conventionally housed pregnant mice will be exposed to pesticides and the gut microbiome and behavior (anxiety, memory, motor performance, social interaction) will be analyzed in their offspring. Also, germ-free mice will be colonized with specific bacteria or bacterial clades to study the causality of the impact of the GM on behavior. The long-term implications for human health are significant – it may be possible to increase tolerance/robustness to pesticide exposure by providing sensitive individuals with probiotics that have select degradation pathways. Moreover, this understanding is important in order to formulate novel preventive strategies including educating health practitioners, families, and public health providers and organizations regarding the potential risks of environmental exposures.

概括 农药在我们的环境中无处不在，并在为数百万人提供服务的饮用水储备中积累 由于潜在的不利健康影响尚未完全了解，因此引起了全世界人民日益关注。 仅2017年，全球就使用了约680万吨农药，其中全球使用量最大的是中国 最近，人们发现农药对微生物有很强的影响。 微生物组成的变化，消灭了整个群落，同时促进了其他群落的生长。 与大脑发育、情绪和行为有关，表明肠道和肠道之间存在密切联系 我们认为可能存在一种未被重视的微生物组成分，对健康不利。 在本提案中，我们将使用综合方法来识别微生物。 具体来说，在目标 1 中，我们将研究农药对神经发育迟缓的敏感性。 产前接触 11 种目标农药对大型明确人类儿童神经发育的影响 母婴微生物群组 (MCMC) 由 3000 对母婴研究参与者组成。 目前定期随访直至孩子满4岁。 对农药接触和儿童早期神经发育数据的分析将确定关键农药 在目标 2 中，我们强调产前接触农药可能会改变儿童的发育。 GM 的组成，随后导致神经发育异常，我们将整合儿童肠道。 孕期接触农药的微生物组数据和儿童神经发育数据 研究产前接触目标农药对儿童肠道微生物组和发育的影响。 该目标将识别与儿童神经发育相关的特定肠道细菌或进化枝。在目标 3 中，我们将。 使用传统和无菌小鼠模型来阐明农药暴露影响的机制 传统饲养的怀孕小鼠的肠道微生物群和行为会暴露于农药和 肠道微生物组和行为（焦虑、记忆、运动表现、社交互动）将在他们的研究中进行分析 此外，无菌小鼠将被特定的细菌或细菌分支定植以研究因果关系。 转基因对人类健康的长期影响可能是重大的。 通过为敏感个体提供益生菌可以提高对农药接触的耐受性/稳健性 此外，这种理解对于制定新颖的方法非常重要。 预防策略，包括对卫生从业人员、家庭和公共卫生提供者进行教育， 组织有关环境暴露的潜在风险的信息。