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.

项目总结/摘要 该提案详细说明了一个为期5年的培训计划，以准备医生候选人，陶（蒂娜）何，职业生涯， 一个独立的，翻译的研究者谁将成为一个领导者在缺铁和贫血领域的 早产该项目将确定肠内补铁作为预防贫血的效果， 通过补充临床和基础科学研究，促进早产儿肠道健康。 所有早产儿都有缺铁的风险。推荐所有早产儿肠内补铁 2-4 mg/kg/天;然而，它们通常以更高的剂量给予，6-10 mg/kg/天。新出现的证据 表明肠内铁可加剧肠道病原体的过度生长并抑制有益细菌。 这种不平衡，或肠道生态失调，肠道炎症和破坏屏障，观察到在坏死 小肠结肠炎，早产儿的一种毁灭性肠道疾病。早产儿的体内定植有较高的 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了 假设高肠内补铁加剧了肠道生态失调、粘膜 炎症和通透性。何博士将通过进行一项随机 研究比较早产儿和早产儿之间的粪便细菌组成、粘膜炎症和屏障功能， 婴儿给予高与低铁方案，并研究细胞因子产生的细胞机制， 使用人3D肠模型的基因表达。在这个项目完成后，何博士将经验丰富， 在1）设计和进行临床研究，2）先进的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 南佛罗里达大学提供的研究人员和教学方法。这个奖项将使她得到更多的保护 时间来发展必要的技能和合作，以建立独立的第4- 5年。何医生会 在Groer博士的主要指导下，Groer博士是转化微生物组和婴儿健康研究的专家， 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高超的 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Dr. Jason Spence（3D肠道模型）。他们把时间花在她的职业发展和研究上 早在这个应用程序之前。他们的指导，快速增长和支持性的研究环境， USF，创新的研究战略和专注的职业发展计划将为以下人员提供强大的平台 博士Ho获得了R 01，以研究不同铁剂量对健康的长期影响， 预防铁缺乏和早产儿贫血。