Early Life Experience Imprints Gut Microbiome in Preterm Infants

描述（由申请人提供）：候选人，小梅聪，博士，注册护士，提出了一个指导病人为导向的研究职业发展奖项目，以提高她的能力，实现她的目标，成为一个独立的临床研究者谁将导致婴儿压力和疼痛领域。随着早产在存活率方面的大幅提高，人们关注的焦点集中在神经系统发病率的显著增加以及与不成熟的神经免疫系统和新生儿重症监护（NICU）住院期间的应激早期生活经历相关的长期不良结局。然而，早期生活压力如何改变婴儿神经发育的机制在很大程度上仍然未知。为了继续实现她的目标，候选人将研究与早期生活压力有关的脑肠道微生物群信号机制的新模型，并使用尖端的微生物分析预测婴儿神经发育（即，肠道微生物组）和免疫炎症生物标志物预测策略（即，粪便细胞因子和钙卫蛋白）。在一项前瞻性纵向研究中提出了三个具体的研究目标，以检查：（1）早产儿在NICU住院前3周内的肠道微生物组模式和粘膜免疫炎症反应;（2）肠道微生物组模式和粘膜免疫炎症反应与早期生活压力的联系;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的联系。 候选人以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/疼痛临床实验研究数据的技能。朝着职业目标的进展需要她在其他内容领域发展专业知识，包括脑肠道信号传导机制的知识和技术以及微生物组分析的基因组方法。一个专家跨学科导师咨询委员会已被选中，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）亨德森和Hussain博士的婴儿压力中涉及的脑肠道信号机制;（3）沃尔什和Graf博士的生物统计学和信息学;及（4）所有导师的传播及撰写资助书。培训和辅导活动将包括正式课程、学习模块、辅导培训、讲习班和其他专业活动。 该项目涉及NINR疾病预防和生活质量改善战略计划的高度优先事项，也是NIH最近倡议“人类微生物组项目”规定的优先事项。“该奖项将使她75%的学术时间用于研究和培训。候选人将在世界一流的研究环境中与导师合作，并成功实现她的目标。研究结果将为R01拨款提案提供初步数据，并将进一步有助于新生儿护理，减少高危婴儿压力的负面影响。.

DESCRIPTION (provided by applicant): 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. .