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、粪便糖组和 对随后接触和不接触的婴儿的家庭环境暴露的测量 从 MABLES 队列中发展出自闭症谱系障碍 (ASD)，这是最常见的一种。 自闭症的共病是胃肠道问题和常见症状 然而，腹泻或便秘几乎都与更严重的症状有关。 迄今为止，关于 ASD 胃肠道功能障碍的研究是在 ASD 诊断后进行的。 已经完成，因此不允许检查胃肠道生态失调之间的时间关系 此外，人们对 ASD 的发病机制还知之甚少。 人们越来越多地认识到微生物群在其中的突出但尚未充分表征的作用。 人类健康已被认识到环境对个体肠道微生物群的影响。 个人资料也受到审查，但关于其影响的工作却很少 利用微生物组的化学暴露。 这是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妊娠研究 项目旨在调查产后早期生活的个人概况的发展 肠道微生物群、环境化学物质对其的影响以及它们与胃肠道的关系 症状以及自闭症的后续发展及其早期症状。 假设是发展中国家常见的环境暴露会影响 在生命的第一年中肠道微生物群和肠道通透性的发展 由此产生的生态失调和肠道“渗漏”会增加患自闭症谱系障碍（ASD）的风险。 建立微生物组和糖组学前沿的跨学科团队 测量，我们将使用最近开发的有效技术来量化粪便乳聚糖 和乳聚糖单体，它们是肠道健康或肠道菌群失调的明显驱动因素 我们将应用创新的机制框架来开发婴儿肠道微生物组。 纳入了自闭症谱系障碍 (ASD) 胃肠道功能障碍中许多已知或可疑的因素，包括 肠道屏障受损，并将接触环境毒素、胃肠道结果和 ASD。在孕产妇和儿童环境、发展中的儿童之间建立联系。 婴儿肠道微生物组、自闭症谱系障碍症状和诊断的出现将为 机制研究探讨如何使婴儿微生物群远离生态失调的发生 在生命的第一年——一个关键的发展时期——对 神经发育结果。