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Enteral Iron Supplementation and Intestinal Health in Preterm Infants

肠内铁补充剂和早产儿肠道健康

基本信息

批准号：
10817288
负责人：
Thao Ho
金额：
$ 5.4万
依托单位：
UNIVERSITY OF SOUTH FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10817288
关键词：
3-Dimensional Actinobacteria class Adult Affect Anemia Attenuated Award Bacteria Basic Science Bifidobacterium Biometry Caring Cell Culture Techniques Cell model Child Child Care Childhood Clinical Clinical Data Clinical Research Clinical Sciences Collaborations Complement Data Data Set Development Development Plans Disease Dose Ensure Enteral Environment Epithelium Erythropoietin Escherichia coli Exposure to Failure Feces Filtration Firmicutes Florida Foundations Funding Future Gene Expression Genomics Goals Gram-Negative Bacteria Growth Health Human IL8 gene Immunity Immunology In Vitro Infant Infant Health Inflammation Inflammatory Interleukin-6 Intestinal Diseases Intestines Iron Iron deficiency anemia Knowledge Lactobacillus Learning Leukocyte L1 Antigen Complex Measures Mentors Mentorship Microbiology Modeling Mucositis Mucous Membrane Necrotizing Enterocolitis Neonatal Nutrient Pathogenicity Patients Permeability Physicians Premature Infant Prevention Production Proteobacteria Proteus Randomized Recommendation Regimen Reporting Research Research Design Research Personnel Risk Salmonella Sampling Scholarship Scientist Secure Shigella Societies Sterility Technology Testing Thinking Third Pregnancy Trimester Time Training United States National Institutes of Health Universities Urine Venous blood sampling Very Low Birth Weight Infant Virulence Work absorption career career development claudin 3 commensal bacteria cytokine design dysbiosis enteric pathogen experience experimental study fecal microbiome fetal gut inflammation gut microbiome improved in vitro Model innovation intestinal epithelium intestinal fatty acid binding protein iron deficiency iron supplementation low income country microbial composition microbiome microbiome analysis mortality neurobehavioral neurodevelopment nutrition pathogen premature preservation prevent research and development response skills three-dimensional modeling translational scientist

项目摘要

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.

项目概要/摘要该提案详细介绍了一项为期 5 年的培训计划，旨在为医生候选人 Thao (Tina) Ho 的职业生涯做好准备一位独立的转化研究者，将成为缺铁和贫血领域的领导者早熟。该项目将确定肠内补铁作为预防贫血的效果，通过互补的临床和基础科学研究来评估早产儿的肠道健康。所有早产儿都有缺铁的风险。建议所有早产儿肠内补充铁剂婴儿2-4毫克/公斤/天；然而，它们的剂量通常较高，即 6-10 毫克/公斤/天。新出现的证据表明肠内铁可以加剧肠道病原体的过度生长并抑制有益细菌。这种不平衡，或者说肠道菌群失调、肠道炎症和屏障破坏，可以在坏死性肠道菌群中观察到。小肠结肠炎，一种破坏性早产儿肠道疾病。早产儿定植有较高的与足月婴儿相比，基线时肠道病原体的百分比。何博士的初步数据导致假设高肠内补铁会加剧肠道菌群失调、粘膜早产儿的炎症和渗透性。何博士将通过进行随机试验来检验这一假设比较早产儿粪便细菌组成、粘膜炎症和屏障功能的研究婴儿接受高铁和低铁治疗，并研究细胞因子产生的细胞机制和使用人类 3D 肠样模型进行基因表达。该项目完成后，何博士将体验到 1) 设计和进行临床研究，2) 高级生物统计分析和解释结果大型临床数据集，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 资助的机构之间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法。这个奖项会让她得到更多的保障在第 4-5 年培养必要的技能和协作能力以建立独立性。何博士将工作在 Groer 博士的指导下，Groer 博士是转化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 Drs.亚当斯和金，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。何博士还建立了卓越的具有以下专业知识的科学顾问团队：Michael Georgieff 博士（铁和神经发育）、Dr. Josef Neu（肠道免疫学）、Sharon Donovan 博士（儿童营养和肠道微生物组）和 Jason Spence（3D 肠道模型）。他们将时间投入到她的职业发展和研究上早在这个应用程序之前就有目标。他们的指导、快速发展和支持性的研究环境南佛罗里达大学的创新研究策略和重点职业发展计划将为学生提供强大的平台何博士获得 R01 来研究不同铁剂量的长期健康影响，以优化预防缺铁和早产儿贫血。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A systematic review of the factors influencing microbial colonization of the preterm infant gut.

DOI：
10.1080/19490976.2021.1884514
发表时间：
2021-01
期刊：
Gut microbes
影响因子：
12.2
作者：
Aguilar-Lopez M;Dinsmoor AM;Ho TTB;Donovan SM
通讯作者：
Donovan SM

Maternal gut microbiota in the postpartum Period: A Systematic review.

DOI：
10.1016/j.ejogrb.2023.03.042
发表时间：
2023-06
期刊：
EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY
影响因子：
2.6
作者：
Weerasuriya, Wasana;Saunders, Julia E.;Markel, Lilla;Xu, Ke;Ho, Thao T. B.;Lemas, Dominick J.;Groer, Maureen W.;Louis-Jacques, Adetola F.
通讯作者：
Louis-Jacques, Adetola F.

The Effects of Genetic Relatedness on the Preterm Infant Gut Microbiota.

遗传相关性对早产儿肠道微生物群的影响。