Enteral Iron Supplementation and Intestinal Health in Preterm Infants

项目摘要/摘要 这份提案详细说明了一项为期5年的培训计划，为医生候选人Thao(Tina)Ho的职业生涯做准备 一位独立的翻译调查员，他将成为缺铁和贫血领域的领导者 早产儿。该项目将确定肠内补铁的效果，作为预防贫血， 通过补充临床和基础科学研究来促进早产儿的肠道健康。 所有早产儿都有缺铁的风险。所有早产儿都推荐肠内补铁 婴儿每天服用2-4毫克/公斤；然而，他们经常服用较高剂量，6-10毫克/公斤/天。新出现的证据 提示肠内铁可以加剧肠道病原体的过度生长，并抑制有益细菌。 在坏死性病变中可观察到这种失衡，即肠道生物失调、肠道炎症和屏障破坏。 小肠结肠炎，一种毁灭性的早产儿肠道疾病。早产儿被寄居在较高的 与足月儿相比，基线时肠道病原体的百分比。何博士的初步数据导致了 假设肠内高铁补充量加剧肠道生物失调，粘膜 早产儿的炎症和通透性。何博士将通过进行一项随机的 早产儿粪便细菌组成、粘膜炎症及屏障功能的比较研究 婴儿给予高铁和低铁方案，并研究细胞因子产生和 利用人体3D肠状骨模型进行基因表达。在这个项目完成后，何博士将会有经验 在1)设计和进行临床研究，2)高级生物统计分析和解释结果 以及3)在3D细胞模型上进行实验。 候选人的独立分析思维将随着NIH资助的定期讨论而增长 由南佛罗里达大学提供的研究人员和教学方法。这一奖励将使她得到更多的保护 有时间发展必要的技能和合作，以在4-5岁之前建立独立性。何博士将会工作 在Groer博士的主要指导下，翻译微生物组和婴儿健康研究方面的专家 许多成功的学员。为了补充她的主要导师，何博士的指导团队，亚当斯博士和金博士， 将在细胞培养技术、微生物学和基因组学方面为她提供支持。何博士还建立了一个卓越的 拥有以下专业知识的科学顾问团队：迈克尔·乔治耶夫博士(铁与神经发育)、 Josef Neu(肠道免疫学)、Sharon Donovan博士(儿童营养和肠道微生物组)和Dr. 杰森·斯宾塞(3D肠道模型)。他们将时间投入到她的事业发展和研究中 早在这项申请之前就有目标。他们的指导，快速增长和支持性的研究环境 USF、创新研究战略和专注的职业发展计划将为以下方面提供强大的平台 何博士将获得一份R01，以研究不同铁质剂量对健康的长期影响，以优化 预防早产儿缺铁和贫血。

Project Summary/Abstract This proposal details a 5-year training plan to prepare the physician candidate, Thao (Tina) Ho, for a career as an independent, translational investigator who will become a leader in the field of iron deficiency and anemia of prematurity. The project will identify the effects of enteral iron supplementation, as prevention for anemia, on intestinal health of preterm infants through complementary clinical and basic science studies. All preterm infants are at risk for iron deficiency. Enteral iron supplementation is recommended to all preterm infants at 2-4 mg/kg/day; however, they are often given at higher doses, 6-10 mg/kg/day. Emerging evidence suggest that enteral iron can exacerbate the overgrowth of enteric pathogens and suppress beneficial bacteria. This imbalance, or intestinal dysbiosis, intestinal inflammation, and disrupted barrier are observed in necrotizing enterocolitis, a devastating intestinal disease of prematurity. Preterm infants are colonized with higher percentage of enteric pathogens at baseline compared to term infants. Dr. Ho’s preliminary data has led to the hypothesis that high enteral iron supplementation exacerbates intestinal dysbiosis, mucosal inflammation and permeability in preterm infants. Dr. Ho will test this hypothesis by conducting a randomized study to compare the fecal bacterial composition, mucosal inflammation and barrier function between premature infants given high vs. low iron regimens and investigating the cellular mechanisms with cytokine production and gene expression using human 3D enteroid models. At the completion of this project, Dr. Ho will be experienced in 1) designing and conducting clinical studies, 2) advanced biostatistical analyses and interpreting the results of large clinical datasets, and 3) performing experiments on 3D cell models. The candidate’s independent analytical thinking will grow with regular discussions among NIH-funded researchers and didactics provided by the University of South Florida. This award will allow her more protected time to develop necessary skills and collaboration to establish independence by the 4-5th year. Dr. Ho will work under the primary mentorship of Dr. Groer, an expert in translational microbiome and infant health research with many successful mentees. To complement her primary mentor, Dr. Ho’s mentoring team, Drs. Adams and Kim, will support her in cell culture techniques, microbiology, and genomics. Dr. Ho also has established a superb team of scientific advisors with the following expertise: Dr. Michael Georgieff (iron and neurodevelopment), Dr. Josef Neu (intestinal immunology), Dr. Sharon Donovan (childhood nutrition and intestinal microbiome), and Dr. Jason Spence (3D intestinal models). They have committed their time to her career development and research goals long before this application. Their mentorships, the fast-growing and supportive research environment at USF, the innovative research strategy, and a focused career development plan will provide a strong platform for Dr. Ho to secure an R01 to investigate the long-term health effects from different iron doses to optimize the prevention of iron deficiency and anemia of prematurity.