Environmental Influence on Infant Microbiome Development and ASD Symptoms

环境对婴儿微生物组发育和 ASD 症状的影响

• 批准号: 9353815
• 负责人: Irva Hertz-Picciotto
• 金额: $ 68.43万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9353815
• 关键词: Actinobacteria class; Autistic Disorder; Bacteria; Bacteroidaceae; Bacteroides; Bacteroidetes; Bifidobacterium; Breastfed infant; Chemical Exposure; Child; Cognitive; Comorbidity; Constipation; Data; Developing Countries; Development; Diagnosis; Diarrhea; Distal; Enterobacteriaceae; Environment; Environmental Exposure; Exposure to; Feces; Food; Functional disorder; Gastrointestinal tract structure; Genes; Genome; Health; Human; Human Milk; Individual; Infant; Intestines; Lactation; Life; Link; Mass Spectrum Analysis; Measurement; Measures; Microbe; Milk; Oligosaccharides; Outcome; Permeability; Polysaccharides; Population; Pregnancy; Proteobacteria; Research; Ribosomes; Risk; Role; Sampling; Siblings; Streptococcaceae; Symptoms; Techniques; Toddler; Toxic Environmental Substances; Work; autism onset; autism spectrum disorder; cohort; critical developmental period; environmental chemical; gastrointestinal; gut microbiome; gut microbiota; high risk infant; household environmental exposure; infancy; innovation; member; microbial; microbiome; microbiota; monomer; next generation sequencing; postnatal; prospective; symptomatology; trend; virtual

ABSTRACT We propose to characterize associations among the fecal microbiome, the fecal glycome, and measures of household environmental exposures in infants who do and do not subsequently develop autism spectrum disorder (ASD) from the MARBLES cohort. One of the most common co-morbidities in autism are gastrointestinal problems, and the presence of frequent symptoms of diarrhea or constipation is associated with more severe symptoms. However, virtually all research on GI dysfunction in ASD to date has been conducted after the ASD diagnosis has been made, thus not allowing for examination of temporal relationships between GI dysbiosis and the onset of ASD. Moreover, few underlying biologic mechanisms have been identified. Increasingly, the prominent but insufficiently characterized, role of the microbiota in human health has been recognized. Environmental influences on individual gut microbiota profiles are also coming under scrutiny, but there has been very little work on the impact of chemical exposures on the microbiome. Taking advantage of data and samples available from a large, prospective pregnancy study of high-risk infant siblings of children with autism, this project seeks to investigate the development in early postnatal life of the individual profiles of the gut microbiome, the environmental chemical influences on these, and their relationship to GI symptoms and to the subsequent development of autism and its early signs. Our overarching hypothesis is that environmental exposures common in developing countries influence the developing intestinal microbiota and intestinal permeability in the first year of life and that the resultant dysbiosis and gut “leakiness” increase risk for development of ASD. With an established interdisciplinary team at the cutting edge of the microbiome and glycome measurement, we will use recently developed effective techniques to quantify fecal milk glycans and milk glycan monomers that are clear drivers for intestinal health or dysbiosis in the developing infant gut microbiome. We will apply an innovative mechanistic framework that incorporates a number of known or suspected factors in GI dysfunction in ASD, including a compromised intestinal barrier, and links exposure to environmental toxins, GI outcomes, and ASD. Establishing associations between the maternal and child environment, the developing infant gut microbiome, and onset of ASD symptomology and diagnosis would set the stage for mechanistic studies examining ways to shift the infant microbiota away from onset of dysbiosis during the first year of life—a critical developmental period—with potential implications for neurodevelopmental outcomes.

抽象的 我们建议表征粪便微生物组，粪便甘氨酸和 随后做和不做的婴儿的家庭环境暴露措施 从大理石队列中发展自闭症谱系障碍（ASD）。最常见的 自闭症的合并症是胃肠道问题，并且经常存在症状 腹泻或便秘与更严重的症状有关。但是，几乎全部 在ASD诊断已有后，已经对ASD的GI功能障碍进行了研究 制作了，因此不允许检查胃肠道疾病之间的临时关系 和ASD的发作。而且，很少有潜在的生物学机制是 确定。越来越多的显着但不充分的表征，微生物群在 人类健康已得到认可。环境对单个肠道菌群的影响 个人资料也受到了审查，但在影响的影响方面很少 微生物组的化学暴露。利用可用的数据和样本 一项针对自闭症儿童的高风险婴儿兄弟姐妹的大型，前瞻性的怀孕研究， 项目旨在调查各个个人概况的早期生活的发展 肠道微生物组，环境化学对它们的影响及其与GI的关系 症状和随后的自闭症及其早期体征的发展。我们的总体 假设是，发展中国家常见的环境暴露会影响 在生命的第一年发展肠道菌群和肠渗透性 由此产生的营养不良和肠道“泄漏”增加了ASD发展的风险。与 在微生物组和Glyce的前沿建立了跨学科团队 测量，我们将使用最近开发的有效技术来量化粪便乳聚糖 和牛奶聚糖单体，它们是肠道健康或营养不良的明显驱动因素 发展婴儿肠道微生物组。我们将应用一个创新的机械框架 在ASD中，在GI功能障碍中纳入了许多已知或怀疑的因素，包括A 肠道障碍妥协，并将暴露与环境毒素，胃肠道结局和 ASD。建立母校和儿童环境之间的关联 婴儿肠道微生物组以及ASD症状和诊断的发作将为 机械研究检查了将婴儿微生物群从营养不良发作中转移的方法 在生命的第一年（一个关键的发展时期），对 神经发育结果。