Early Life Experience Imprints Gut Microbiome in Preterm Infants

摘要 候选人丛晓梅，博士，RN，提出了一种以患者为导向的导师研究生涯 发展奖项目，以提高她的能力，实现她成为一名独立临床医生的目标 将领导婴儿压力和疼痛领域的研究人员。随着早产存活率的大幅提高， 人们关注的焦点是神经系统发病率和长期不良后果的显著增加。 重症新生儿早期生活经历与神经免疫系统不成熟的关系 护理(NICU)留下来。然而，早期生活应激如何改变婴儿神经发育的机制仍然存在 很大程度上是未知的。为了继续朝着她的目标前进，候选人将研究大脑的新模型-- 肠道微生物区系参与早期生活应激的信号机制及婴儿神经发育的预测 使用尖端微生物分析(即肠道微生物组)和免疫炎症生物标记物 预测策略(即粪便细胞因子和钙保护素)。提出了三个具体的研究目标。 前瞻性纵向研究：(1)早产儿肠道微生物菌群模式与粘膜免疫功能 在NICU住院的前3周的炎症反应；(2)肠道微生物组模式与 黏膜免疫-炎症反应与早期生活应激；以及(3)肠道微生物组和 粘膜免疫-炎症反应与自主神经和神经行为结果。 应聘者之前的培训和研究经验为她提供了计划、实施和 分析婴儿压力/疼痛的临床实验研究数据。要实现职业目标，需要 她将在其他内容领域发展专业知识，包括大脑-肠道信号传递的知识和技术 微生物组分析的机理和基因组方法。专业的跨学科导师咨询 委员会已经选出，候选人将通过实践经验获得以下知识：(1) Graf和Gregory博士的微生物组和基因组学知识和技术；(2)大脑-肠道的机制 亨德森和侯赛因博士的《婴儿应激信号传递》；(3)生物统计学和信息学。 沃尔什和格拉夫；以及(4)所有导师的传播和赠款写作。培训和指导活动将 包括正式课程、学习模块、指导培训、研讨会和其他专业活动。 该项目涉及NINR疾病预防和生活质量战略计划的高度优先事项 改进，也是美国国立卫生研究院最近的一项倡议--“人类微生物组项目”--所明确的优先事项。这个 获奖将使她75%的学术时间投入到研究和培训中。候选人会成功的 在世界一流的研究环境中与导师一起成功地实现了她的目标。研究结果将 为R01赠款提案提供初步数据，并将进一步促进新生儿护理在减少 压力对高危婴儿的负面影响。 。

Abstract The candidate, Xiaomei Cong, PhD, RN, proposes a Mentored Patient-Oriented Research Career Development Award project to enhance her ability to achieve her goal of becoming an independent clinical investigator who will lead the field of infant stress and pain. With preterm birth substantial gains in survival, concerns have focused on significant increases in neurological morbidity and long-term adverse outcomes related to the immature neuro-immune systems and stressful early life experience in the neonatal intensive care (NICU) stay. However, how the mechanisms of early life stress alter infant neurodevelopment remains largely unknown. To continue progress towards her goal, the candidate will examine the new models of brain- gut-microbiota signaling mechanism involved in early life stress and prediction of infant neurodevelopment using cutting-edge microbiological analysis (i.e., gut microbiome) and immune-inflammatory biomarker prediction strategies (i.e., fecal cytokines and calprotectin). Three specific research aims are proposed in a prospective longitudinal study to examine: (1) preterm infants' gut microbiome patterns and mucosal immune- inflammatory responses over the first 3 weeks of NICU stay; (2) the linkage of gut microbiome patterns and mucosal immune-inflammatory responses with early life stress; and (3) the linkage of gut microbiome and mucosal immune-inflammatory responses with autonomic nervous and neurobehavioral outcomes. The candidate's previous training and research experience provided her skills to plan, implement, and analyze data from clinical experimental studies in infant stress/pain. Progress toward the career goals requires her to develop expertise in additional content areas including knowledge and technology of brain-gut signaling mechanism and genomic approaches to microbiome analysis. An expert interdisciplinary mentor advisory committee has been selected and the candidate will gain knowledge by hands-on experience of: (1) microbiome and genomics knowledge and technology by Drs. Graf and Gregory; (2) mechanism of brain-gut signaling involved in infant stress by Drs. Henderson and Hussain; (3) biostatistics and informatics by Drs. Walsh and Graf; and (4) dissemination and grant writing by all mentors. Training and mentoring activities will include formal coursework, learning modules, mentored training, workshops, and other professional activities. The project addresses a high priority of the NINR strategic plan of disease prevention and quality of life improvement and also a priority of NIH specified by a recent initiative, the "Human Microbiome Project." The award will enable 75% of her academic time to be devoted to research and training. The candidate will work with mentors in a world-class research environment and successfully reach her goals. Study results will provide the preliminary data for an R01 grant proposal and will further contribute to neonatal care in reducing negative consequences of stress in high-risk infants. .