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

描述早产儿皮肤微生物组的特征以及新生儿迟发性败血症 (LOS) 之前的微生物变化

• 批准号: 10664071
• 负责人: Jennifer Jane Schoch
• 金额: $ 16.16万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10664071
• 关键词: 16S ribosomal RNA sequencing; Address; Affect; Antibiotics; Antisepsis; Award; Bacteria; Bathing; Bioinformatics; Birth; Candida; Caring; Catheters; Cesarean section; Childhood; Clinical; Clinical Trials; Collection; Control Groups; Corynebacterium; Cutaneous; Data; Dermatology; Development; Disease; Early identification; Environment; Ethnic Origin; Evolution; Exhibits; Failure; Florida; Future; Genus staphylococcus; Gestational Age; Goals; Hospitalization; Hospitals; Humidity; Incidence; Infant; Intervention; K-Series Research Career Programs; Klebsiella; Knowledge; Laboratories; Lactobacillus; Lead; Leadership; Learning; Life; Medicine; Mentors; Metagenomics; Methods; Microbe; Natural History; Neonatal; Outcome; Outpatients; Parents; Pathogenicity; Physicians; Predisposition; Premature Infant; Prevention; Prevention strategy; Race; Research; Research Activity; Research Design; Resources; Risk; Role; Sample Size; Sampling; Science; Scientist; Sepsis; Serratia; Shotguns; Site; Skin; Streptococcus; Swab; Testing; Therapeutic; Training; Training Activity; Training Programs; Translational Research; Universities; Very Low Birth Weight Infant; Work; career; career development; career networking; cohort; college; design; experience; extreme prematurity; feeding; gut microbes; indexing; innovation; insight; large datasets; late onset sepsis; metagenomic sequencing; microbial; microbiome; microbiome composition; microbiome research; microbiota transplantation; mortality; neonatal sepsis; novel; opportunistic pathogen; pathogen; pathogen exposure; pathogenic bacteria; perinatal complications; preterm newborn; programs; recruit; sex; skills; skin barrier; skin microbiome; skin microbiota; skin organogenesis; statistics; surveillance strategy; vaginal microbiota

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.

项目摘要 尽管最近对微生物组的重视，但很少有婴儿皮肤微生物组的研究; 在早产儿中进行。目前，我们对正常进化的认识存在很大差距， 早产儿皮肤微生物组从出生到一个独立的，位点特异性的皮肤微生物组。 初步研究表明，早产儿的微生物多样性有限， 与足月婴儿相比，皮肤微生物。这种缺乏强大的，多样化的皮肤微生物组可能会使 早产儿易受致病性皮肤细菌的影响，导致疾病，特别是新生儿败血症。的 这项指导性职业发展奖的研究目标是：1）描述建立 从出生到4周的早产儿队列中的新生儿皮肤微生物组，并与人口统计学和 临床变量，2）招募一组足月婴儿以确定早产婴儿皮肤微生物组是否 与足月婴儿显著不同，以及3）在晚发型中用皮肤微生物组分析培养的病原体 新生儿败血症（LOS）。我们的方法代表了从目前可用的研究，其中提供了一个出发点。 新生儿皮肤微生物组的机会性采样，而不是在规定的时间点采样。本研究将 通过在出生后系统地对早产儿皮肤微生物组进行采样来垂直推进该领域。的作用 新生儿败血症中的皮肤微生物组也没有描述，本研究的设计将提供更好的 了解迟发性脓毒症前皮肤微生物组的变化。这些目标将共同提供 了解早产儿皮肤微生物组的正常和异常发育。今后的研究将 通过治疗和预防策略利用新生儿皮肤微生物组，以降低LOS的发生率。 这个K23是在我的KL 2奖励下开始的培训计划的下一个合乎逻辑的步骤，也是我的最后一步。 转变为独立的医生科学家。本提案介绍了有指导的研究和培训活动 旨在启动一项新的新生儿皮肤微生物组研究计划，这是儿科领域的第一个 皮肤科。在我的指导团队的协助下，需要五个培训和职业发展目标， 完成这个。这些包括：扩展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 先进的宏基因组分析），学习领导一个独立的实验室，并扩大我的专业网络 微生物组科学中。佛罗里达大学提供了一个丰富的环境与专业知识，在新生儿 微生物组学和宏基因组学，理想地扩展我以前的工作，因为我开发了一种新的新生儿皮肤微生物组 研究计划。UF的资源将通过额外的皮肤微生物组专业知识和 来自贝勒医学院和Diversigen Inc.的Pammi博士的实验室资源。