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

项目摘要 当婴儿离开无菌（或接近无菌）环境时， 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），而且是真核病毒和噬菌体（病毒组）的多样化聚生体。 这些生命早期的微生物群落对健康的婴儿发育至关重要，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非常重要的。 没有被很好地理解。肠道微生物被认为是从母亲和环境中传播的。我们 在婴儿粪便中发现了大量噬菌体（感染细菌的病毒） 在它们生命的前96小时，然后描述了肠道噬菌体之间的捕食者-猎物动态 和细菌在婴儿随后的头两年的生活。以确定是否有子宫内储库 对于这些不同的噬菌体群落，我们表征了羊膜上皮细胞的病毒组和细菌微生物群， 从24例无并发症的足月妊娠中剖腹产时获得的液体。羊膜腔细菌序列 液体与单独缓冲液污染对照中的液体无法区分， 羊水，我们没有发现任何证据表明样本中存在核心病毒群落。这些数据强烈 这表明羊水不会产生基础细菌微生物组或病毒组。 多方面的证据表明，环境是塑造的重要影响， 细菌微生物组和病毒组：肠道微生物群落的内容与地理，宿主遗传学 只占细菌微生物群变异的一小部分，婴儿的细菌 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 环境来源的大多数微生物殖民足月婴儿。我们现在不得不 对环境进行系统的检查，并确定这些子宫外照射对 新生儿的殖民化。我建议收集一个出生队列，并测试我的假设，即一部分的 婴儿肠道病毒组和细菌微生物组是从环境中获得的。因为持久的 这些基础微生物类群对婴儿的影响，关键是要了解它们是如何获得的。 因此，可以提出适当的建议和干预措施，以优化这一重要事件。

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.