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

项目摘要 随着婴儿离开不育症(或接近不育症)，肠道经历了深刻的生态转变 子宫，并获得它的微生物群。微生物群不仅包括细菌群落 (细菌微生物组)，但也是真核病毒和噬菌体(病毒体)的不同联合体。 这些生命早期的微生物群落对婴儿的健康发育至关重要，包括塑造生长， 抗感染、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群和病毒体的获取和早期成熟 不是很清楚。肠道微生物被认为是从母亲和环境中传播的。我们 婴儿粪便中的噬菌体(感染细菌的病毒)种类繁多 在它们生命的最初96小时内，然后描述了肠道噬菌体之间的捕食者-猎物动态 在接下来的头两年里，婴儿体内的细菌。以确定是否存在宫内储存库 对于这些不同的噬菌体群落，我们描述了羊水中的病毒体和细菌微生物区系。 24例无并发症足月妊娠剖宫产取液。羊水中的细菌序列 液体与单独缓冲液污染对照组的病毒读数无法区分，病毒读取在 羊水，我们在样本中没有发现核心病毒群落的证据。这些数据强烈地 提示羊水不会产生细菌微生物群或病毒体。 多种多样的证据表明，环境是影响人类健康的重要因素。 细菌微生物群和病毒体：肠道微生物群落的含量因地理、宿主遗传而异 只占细菌微生物群中可变性的一小部分，而婴儿的细菌 微生物群和病毒体与它们的母亲几乎没有重叠。然而，我们不知道 大多数定植在婴儿身上的微生物的环境来源。我们现在被迫进行一场 对环境进行系统检查，并确定这些体外暴露对 新生儿的移居化。我建议组建一个出生队列，并检验我的假设 婴儿肠道病毒群和细菌微生物群是从环境中获得的。因为经久不衰 这些建立的微生物分类群对婴儿的影响，关键是要了解它们是如何获得的 发生，以便能够提出适当的建议和干预措施，以优化这一重要活动。

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.