Role of Environmental Exposures on the Infant Gut Bacterial Microbiome and Virome

环境暴露对婴儿肠道细菌微生物组和病毒组的作用

• 批准号: 10364758
• 负责人: Lori R Holtz
• 金额: $ 64.66万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10364758
• 关键词: Adult; Adverse event; Affect; Amniotic Fluid; Bacteria; Bacteriophages; Birth; Buffers; Cesarean section; Child; Childhood; Communities; Complex; Data; Development; Disease; Enrollment; Environment; Environmental Exposure; Event; Exposure to; Feces; Genetic; Geography; Germ-Free; Gestational Age; Growth; Health; Home; Home environment; Hospitals; Hour; Household; Human; Human Biology; Human Genetics; Hypersensitivity; Infant; Infant Development; Inflammation; Intervention; Knowledge; Life; Microbe; Mothers; Necrotizing Enterocolitis; Neonatal; Neonatal Intensive Care Units; Newborn Infant; Nurses; Obesity; Perinatal; Pregnancy; Premature Infant; Prospective Studies; Reagent; Recommendation; Resistance to infection; Rest; Role; Sampling; Shapes; Siblings; Source; Specimen; Sterility; Structure; Testing; Time; Twin Multiple Birth; Uterus; Viral; Virus; bacteriome; cohort; dysbiosis; geographic difference; gut bacteria; gut colonization; gut microbes; gut microbiota; immune function; in utero; infancy; inter-individual variation; member; microbial; microbial community; microbiome; microbiota; mouse model; neonatal period; neonate; next generation sequencing; nutrition; transmission process; virome

Project Summary The gut undergoes a profound ecological transition as the infant leaves the sterile (or near sterile) womb and acquires its microbiome. The microbiome encompasses not only the community of bacteria (bacterial microbiome), but also a diverse consortium of eukaryotic viruses and bacteriophages (virome). These early-in-life microbial communities are critical for healthy infant development including shaping growth, infection resistance, inflammation, and immune function. Alterations in these communities set the stage for neonatal adverse events, such as necrotizing enterocolitis, and later-in-life diseases such as obesity and allergies. Remarkably, the acquisition and early maturation of neonatal gut bacterial microbiome and virome are not well understood. Gut microbes are thought to be transmitted from the mother and the environment. We demonstrated a tremendous diversity of bacteriophages (viruses that infect bacteria) in stools from infants during their first 96 hours of life and then characterized a predator-prey dynamic between gut bacteriophages and bacteria in infants over the subsequent first two years of life. To determine if there is an in utero reservoir for these diverse bacteriophage communities, we characterized the virome and bacterial microbiota of amniotic fluid obtained at Cesarean section from 24 uncomplicated term pregnancies. Bacterial sequences in amniotic fluid were indistinguishable from those in buffer-alone contamination controls, viral reads were sparse in the amniotic fluid, and we found no evidence of a core viral community across samples. These data strongly suggest that the amniotic fluid does not give rise to the founding bacterial microbiome or virome. Multiple lines of evidence suggest that the environment is an important influence in shaping the bacterial microbiome and virome: gut microbial communities differ in content with geography, host genetics account for only a small fraction of the variability seen in bacterial microbiomes, and infants’ bacterial microbiomes and viromes have little overlap with those of their mothers. However, we do not know the environmental source of most microbes that colonize the term infant. We are now compelled to conduct a systematic examination of the environment and determine the contribution of these ex utero exposures on colonization of the neonate. I propose to assemble a birth cohort and test my hypothesis that a portion of the infant gut virome and bacterial microbiome are acquired from the environment. Because of the enduring consequences of these founding microbial taxa for the infant, it is critical to understand how their acquisition occurs so that appropriate recommendations and interventions can be made to optimize this important event.

项目摘要 当婴儿离开无菌（或靠近无菌）时，肠道经历了深刻的生态过渡 子宫并获得其微生物组。微生物组不仅包括细菌群落 （细菌微生物组），以及真核病毒和噬菌体（病毒蛋白酶）的潜水财团。 这些早期的微生物群落对于健康的婴儿发展至关重要，包括塑造增长， 感染性，感染和免疫功能。这些社区的改变为 新生儿不良事件，例如坏死性小肠结肠炎，以及肥胖和肥胖等后期疾病 过敏。 值得注意的是，新生儿肠道细菌和病毒蛋白的获取和早期成熟是 不太了解。肠道微生物被认为是从母亲和环境中传播的。我们 在婴儿的粪便中表现出众多噬菌体（感染细菌的病毒）的多样性 在生命的最初96小时中，然后表征了肠道噬菌体之间的捕食者捕获动态 随后的两年中，婴儿的细菌和细菌。确定子宫库中是否有一个 对于这些潜水员菌群群落，我们表征了羊膜的病毒蛋白和细菌菌群 从24个简单的术语妊娠中获得的剖宫产的液体。羊水中的细菌序列 流体与在污染控制中没有区别的流体，病毒读数稀疏 羊水，我们没有发现样品中核心病毒群落的证据。这些数据强烈 表明羊水不会引起基础细菌微生物组或病毒蛋白。 多种证据表明，环境在塑造塑造方面是重要的影响 细菌微生物组和病毒蛋白：肠道微生物群落在与地理位置的内容上不同，宿主遗传学 仅占细菌微生物中可变性的一小部分和婴儿的细菌 微生物组和病毒瘤与母亲的重叠几乎没有重叠。但是，我们不知道 大多数微生物的环境来源，这些微生物将术语定居。我们现在被迫进行 对环境的系统检查并确定这些前子宫暴露对 新生儿的殖民化。我建议组装一个出生队列，并测试我的假设 婴儿肠道病毒组和细菌微生物组是从环境中获取的。因为持久 这些为婴儿创建微生物分类群的后果，重要的是要了解他们的收购如何 发生，以便可以提出适当的建议和干预措施来优化这一重要事件。