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

摘要 杀虫剂在我们的环境中无处不在，并积累在供应数百万人的饮用水储备中 由于尚未完全了解其对健康的潜在不利影响，因此引起了越来越多的关注。 仅2017年，全球农药使用量约680万吨，其中世界上使用量最大的是中国 还有美国。最近，人们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。微生物组成的变化已经 与大脑发育、情绪和行为有关，这表明肠道和 大脑。我们推测可能存在一种未被认识到的微生物组成分对健康不利。 农药暴露的影响。在这项提案中，我们将使用一种综合的方法来鉴定微生物 农药对神经发育迟缓的易感性成分。具体来说，在目标1中，我们将调查 产前暴露于11种靶向杀虫剂对大型明确人群儿童神经发育的影响 母子微生物群组(MCMC)由3000对母子组成。研究参与者是 目前定期跟踪，直到儿童达到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，我们假设产前接触杀虫剂可以改变 GM的组成，并随后导致神经发育异常。我们将整合孩子们的直觉 孕期母亲接触农药的微生物组数据和儿童神经发育数据 研究产前暴露于靶向农药对儿童肠道微生物群和发育的影响。 这一目标将识别与儿童神经发育相关的特定肠道细菌或分支。在《目标3》中，我们将 使用常规和无菌小鼠模型来阐明接触杀虫剂可能影响的机制 肠道微生物群和行为。常规饲养的怀孕小鼠将暴露于杀虫剂和 肠道微生物群和行为(焦虑、记忆、运动表现、社交)将在他们的 后代。此外，无菌小鼠将被特定的细菌或细菌分支定居，以研究其因果关系。 关于通用汽车对行为的影响。这对人类健康的长期影响是重要的--它可能是 可能通过向敏感个体提供益生菌来提高对农药暴露的耐受性/稳健性 它们有精选的退化途径。此外，这种理解对于写小说也很重要。 预防战略，包括教育卫生从业者、家庭和公共卫生提供者以及 关于环境暴露的潜在风险的组织。

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.