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.

总结 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 由于对潜在的不利健康影响尚未完全了解， 仅在2017年，全球就使用了约680万吨农药，其中世界上最大的使用量是在中国 和美国最近发现杀虫剂对微生物有很强的影响， 社区，消灭整个分支，同时促进其他分支的增长。微生物组成的变化 与大脑发育，情绪和行为有关，这表明肠道和大脑之间有很强的联系。 个脑袋我们假设可能存在一种未被重视的微生物组成分， 农药暴露的影响。在本提案中，我们将使用一种全面的方法来识别微生物 农药敏感性的神经发育迟缓的组成部分。具体来说，在目标1中，我们将研究 产前暴露于11种目标农药对儿童神经发育的影响 母亲和儿童微生物组队列（MCMC）由3000对母亲和儿童组成。研究参与者是 目前定期随访，直至儿童年满4岁。综合人工智能 对农药暴露和儿童早期神经发育数据的分析将确定关键的农药， 对儿童发展产生负面影响。在目标2中，我们假设产前暴露于杀虫剂可以改变胎儿的性别。 GM的组成，并随后导致异常的神经发育。我们会把孩子的肠子 微生物组数据，包括怀孕期间母亲接触农药和儿童神经发育数据， 调查产前暴露于目标农药对儿童肠道微生物组和发育的影响。 该目标将确定与儿童神经发育相关的特定肠道细菌或分支。在目标3中，我们 使用传统的和无菌的小鼠模型来阐明农药暴露可以影响 肠道微生物组和行为。常规饲养的怀孕小鼠将暴露于杀虫剂， 肠道微生物组和行为（焦虑，记忆，运动表现，社会互动）将在他们的研究中进行分析。 后代此外，无菌小鼠将与特定的细菌或细菌分支定殖，以研究因果关系 转基因对行为的影响。对人类健康的长期影响是重大的-它可能是 通过向敏感个体提供益生菌，可能增加对农药暴露的耐受性/稳健性 有选择的降解途径。此外，这种理解是重要的，以制定新的 预防战略，包括教育卫生从业人员、家庭和公共卫生提供者， 组织关于环境暴露的潜在风险。