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: 9973474
• 负责人: Lori R Holtz
• 金额: $ 63.31万
• 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/9973474
• 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 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.

项目概要 当婴儿离开无菌（或接近无菌）时，肠道经历了深刻的生态转变 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），也是真核病毒和噬菌体（病毒组）的多样化组合。 这些生命早期的微生物群落对于婴儿的健康发育至关重要，包括塑造生长、 感染抵抗力、炎症和免疫功能。这些社区的变化为 新生儿不良事件，如坏死性小肠结肠炎，以及晚年疾病，如肥胖症和 过敏。 值得注意的是，新生儿肠道细菌微生物组和病毒组的获得和早期成熟是 不太理解。肠道微生物被认为是从母亲和环境传播的。我们 证明婴儿粪便中的噬菌体（感染细菌的病毒）具有巨大的多样性 在它们生命的最初 96 小时内，然后表征肠道噬菌体之间的捕食者-猎物动态 以及婴儿出生后头两年的细菌。确定是否存在子宫内储库 对于这些不同的噬菌体群落，我们描述了羊膜动物的病毒组和细菌微生物群 24 例简单的足月妊娠在剖腹产时获得的液体。羊膜中的细菌序列 液体与仅缓冲液污染对照中的液体无法区分，病毒读数在 羊水中，我们没有发现样本中存在核心病毒群落的证据。这些数据强烈 表明羊水不会产生基础细菌微生物组或病毒组。 多种证据表明，环境对于塑造人的性格具有重要影响。 细菌微生物组和病毒组：肠道微生物群落的内容因地理、宿主遗传学而异 仅占细菌微生物组和婴儿细菌组变异性的一小部分 微生物组和病毒组与其母亲的微生物组和病毒组几乎没有重叠。然而，我们不知道 足月婴儿中大多数微生物的环境来源。我们现在被迫进行一次 对环境进行系统检查并确定这些宫外暴露对环境的影响 新生儿的定植。我建议组建一个出生队列并检验我的假设： 婴儿肠道病毒组和细菌微生物组是从环境中获得的。因为历久不衰 这些创始微生物类群对婴儿的影响，了解它们是如何获得的至关重要 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。