Environmental Influence on Infant Microbiome Development and ASD Symptoms

摘要 我们建议描述粪便微生物群、粪便糖类和粪便糖类之间的联系。 随后进行和不进行家庭环境暴露的婴儿的测量方法 从大理石队列中发展出自闭症谱系障碍(ASD)。最常见的一种 自闭症的共病是胃肠道问题，并存在频繁的症状 腹泻或便秘与更严重的症状有关。然而，几乎所有的 到目前为止，ASD的胃肠功能障碍的研究是在ASD诊断为 因此不允许检查胃肠道生物失调之间的时间关系 和ASD的发病。此外，几乎没有潜在的生物机制被 已确认身份。微生物区系在生物多样性中的作用日益突出，但还不够明确 人类的健康已经得到了认可。环境对个体肠道微生物区系的影响 个人资料也受到了审查，但关于 微生物群上的化学物质暴露。利用以下网站提供的数据和样本 这是一项针对自闭症儿童高危婴儿兄弟姐妹的大型前瞻性怀孕研究 该项目旨在调查儿童出生后早期生活的发展情况。 肠道微生物群、环境化学对其的影响及其与胃肠道感染的关系 这与自闭症的症状和随后的发展及其早期症状有关。我们最重要的是 假说是发展中国家常见的环境暴露会影响 在生命的第一年发育肠道微生物区系和肠道通透性 由此导致的生物失调和肠道“渗漏”增加了ASD发展的风险。带着一个 在微生物组和甘露糖的前沿建立了跨学科团队 为了测量，我们将使用最新开发的有效技术来量化粪便牛奶多糖 和牛奶葡聚糖单体，它们是肠道健康或肠道生物失调的明显驱动因素 发育中的婴儿肠道微生物群。我们将应用创新的机制框架， 合并了一些已知或可疑的因素导致ASD的胃肠道功能障碍，包括 肠道屏障受损，并与暴露于环境毒素、GI结局和 ASD.建立母婴环境、发展中的 婴儿肠道微生物组，ASD症状和诊断的出现将为 研究如何使婴儿微生物区系远离生物失调的机制研究 在生命的第一年--一个关键的发展时期--可能对 神经发育结果。

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.