Characterizing the preterm infant skin microbiome and microbial shifts that precede neonatal late onset sepsis (LOS)

项目总结 尽管最近强调了微生物组，但对婴儿皮肤微生物组的研究很少；更少 已在早产儿身上进行过。目前，我们对正常进化的认识存在着很大的差距 从早产儿出生到独立的、特定部位的皮肤微生物组。 初步研究表明，早产儿微生物多样性有限，优势种不同 皮肤微生物与足月婴儿的比较。缺乏强健、多样的皮肤微生物群可能会使 早产儿容易感染致病的皮肤细菌，特别是新生儿败血症。这个 这个辅导式职业发展奖的研究目标是：1)描述 出生至4周的早产儿队列中的新生儿皮肤微生物组与人口学和 临床变量，2)招募一组足月婴儿来确定早产儿皮肤微生物组是否 与足月儿明显不同，以及3)分析迟发性皮肤微生物群中培养的病原体 新生儿败血症(LOS)。我们的方法与目前可用的研究有所不同，这些研究提供了 对新生儿皮肤微生物群进行机会性采样，而不是在确定的时间点采样。这项研究将 垂直推进场，通过在出生后系统地采样早产儿皮肤微生物群来进行。美国政府的角色 皮肤微生物组在新生儿败血症中也没有被描述，本研究的设计将提供更好的 了解迟发性败血症前皮肤微生物群的变化。这些目标加在一起将提供 洞察早产儿皮肤微生物组的正常和异常发育。到那时，未来的研究将 通过治疗和预防策略利用新生儿皮肤微生物群来降低LOS的发生率。 这个K23是我在KL2奖下开始的培训计划的下一个合乎逻辑的步骤，也是我 成为一名独立的内科科学家。本提案描述了有指导的研究和培训活动。 旨在启动一项新颖的新生儿皮肤微生物组研究计划，在儿科领域首创 皮肤科。在我的指导团队的帮助下，需要五个培训和职业发展目标，以 做到这一点。这些包括：扩大我对研究设计的理解，加深我对 微生物组和相关实验室科学，获得统计学/生物信息学的工作知识(包括 高级元基因组分析)，学习领导独立实验室，并扩大我的专业网络 在微生物组科学中。佛罗里达大学提供了丰富的环境，拥有新生儿方面的专业知识 微生物组和元基因组学，理想地扩展我之前的工作，因为我开发了一个新的新生儿皮肤微生物组 研究计划。UF的资源将通过更多的皮肤微生物组专业知识和 来自贝勒医学院和Diversigen Inc.Pammi博士的实验室资源。

PROJECT SUMMARY Despite recent emphasis on the microbiome, there are few skin microbiome studies in infants; even fewer have been performed in preterm infants. Currently, there is a significant gap in our knowledge of the normal evolution of the preterm infant skin microbiome from birth to an independent, site-specific cutaneous microbiome. Preliminary studies show that preterm infants have limited microbial diversity and different predominant cutaneous microbes compared to full-term infants. This lack of a robust, diverse skin microbiome may render preterm infants susceptible to pathogenic skin bacteria that cause disease, particularly neonatal sepsis. The research goals of this mentored career-development award are to: 1) characterize the establishment of the neonatal skin microbiome in a cohort of preterm infants from birth to 4 weeks and compare to demographic and clinical variables, 2) recruit a cohort of term infants to determine if the preterm infant skin microbiome is significantly different than term infants, and 3) analyze cultured pathogens with the skin microbiome in late-onset neonatal sepsis (LOS). Our methods represent a departure from the currently available studies, which provide opportunistic sampling of the neonatal skin microbiome rather than sampling at defined timepoints. This study will vertically-advance the field by sampling the preterm skin microbiome systematically after birth. The role of the skin microbiome in neonatal sepsis has also not been described, and the design of this study will provide a better understanding of changes in the skin microbiome before late onset sepsis. Together, these aims will provide insight into the normal and abnormal development of the preterm infant skin microbiome. Future studies will then leverage the neonatal skin microbiome via therapeutic and preventative strategies to lower the incidence of LOS. This K23 is the next logical step in the training program started under my KL2 award, and the final step in my transition to an independent physician scientist. This proposal describes mentored research and training activities designed to launch a novel neonatal skin microbiome research program, the first in the field of pediatric dermatology. Five training and career development goals, facilitated by my mentoring team, are required to accomplish this. These include: extend my understanding of research design, deepen my knowledge of microbiome and relevant laboratory science, gain working knowledge of statistics/bioinformatics (including advanced metagenomic analyses), learn to lead an independent laboratory, and expand my professional network within microbiome science. The University of Florida provides a rich environment with expertise in the neonatal microbiome and metagenomics, ideal to extend my previous work as I develop a novel neonatal skin microbiome research program. The resources at UF will be augmented by additional skin microbiome expertise and laboratory resources from Dr. Pammi at Baylor College of Medicine and Diversigen Inc.