Enteral Iron Supplementation and Intestinal Health in Preterm Infants

肠内铁补充剂和早产儿肠道健康

• 批准号: 10222776
• 负责人: Thao Ho
• 金额: $ 19.59万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10222776
• 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 Research; Clinical Sciences; Collaborations; Complement; Data; Data Set; Development; Development Plans; Disease; Dose; Ensure; Enteral; Environment; Epithelial; 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; 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 microbiome; improved; in vitro Model; inflammatory disease of the intestine; 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

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.

项目摘要/摘要 该建议详细介绍了一项为期5年的培训计划，以准备身体候选人Thao（Tina）Ho，从事职业 一个独立的翻译调查员，将成为铁缺乏症和贫血领域的领导者 早熟。该项目将确定补充肠铁的影响，作为贫血的预防，对 通过完整的临床和基础科学研究对早产儿的肠道健康。 所有早产儿都有缺铁的风险。建议所有早产供肠内补充 婴儿为2-4 mg/kg/天；但是，通常以更高剂量的6-10 mg/kg/天给予它们。新兴证据 表明肠铁会加剧肠道病原体的过度生长并抑制有益细菌。 在坏死中观察到这种不平衡或肠道营养不良，肠道注射和障碍的破坏 小肠结肠炎，一种毁灭性的早产肠道疾病。早产婴儿被殖民 与期限婴儿相比，基线时肠道病原体的百分比。 Ho博士的初步数据导致了 假设高肠内补充剂加剧了肠道营养不良，粘膜 早产儿的炎症和渗透性。 Ho博士将通过进行随机进行检验 研究比较粪便细菌组成，粘膜感染和过早之间的屏障功能 婴儿对低铁治疗方案的婴儿，并研究细胞因子产生和 使用人类3D肠模型的基因表达。该项目完成后，Ho博士将经验丰富 在1）设计和进行临床研究，2）高级生物统计分析并解释结果 大型临床数据集和3）对3D细胞模型进行实验。 候选人的独立分析思维将通过NIH资助的定期讨论增长 南佛罗里达大学提供的研究人员和教学法。这个奖项将使她更受保护 是时候发展必要的技能和协作以在第4-5岁之前建立独立。 Ho博士将工作 在Groer博士的主要心态下，Groer博士是翻译微生物组和婴儿健康研究的专家 许多成功的导师。为了补充她的主要导师，Ho博士的心理团队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支持她。 Ho博士还建立了一流的 科学顾问团队具有以下专业知识：Michael Georgieff博士（铁和神经发育），博士 Josef Neu（肠道免疫学），Sharon Donovan博士（儿童营养和肠道微生物组）和博士 Jason Spence（3D肠模型）。他们花了时间去做她的职业发展和研究 在此应用之前很久。他们的攻击性，快速增长和支持性的研究环境 USF，创新的研究策略以及一项重点的职业发展计划将为 Ho博士确保R01来研究不同铁剂量的长期健康影响，以优化 预防铁缺乏症和早产性贫血。