Integrating Novel Physiological Biomarkers of Feeding Intolerance in Preterm Infants

整合早产儿喂养不耐受的新型生理生物标志物

• 批准号: 10739943
• 负责人: Eric Brum Ortigoza
• 金额: $ 16.74万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10739943
• 关键词: 16S ribosomal RNA sequencing; Abdomen; Address; Age; Area; Bioinformatics; Biological Markers; Blinded; Catheters; Child Health; Clinical; Clinical Research; Collection; Complex; Computer Models; Cutaneous; Data; Dedications; Development; Development Plans; Enteral Feeding; Environment; Feces; Fostering; Foundations; Funding; Gastrointestinal Motility; Gastrointestinal Physiology; Goals; Growth; Health; Hospitals; Ileus; Infant; Interruption; Intestinal Obstruction; Intestinal Perforation; Intravenous; K-Series Research Career Programs; Knowledge; Lead; Leadership; Learning; Length of Stay; Longitudinal cohort study; Machine Learning; Malnutrition; Master of Science; Measurement; Measures; Medical center; Mentors; Mesentery; Methods; Monitor; Morbidity - disease rate; Multicenter Studies; Near-Infrared Spectroscopy; Necrotizing Enterocolitis; Neonatal; Neonatal Intensive Care; Neonatal Intensive Care Units; Outcome; Parenteral Nutrition; Pathologic; Pathology; Physicians; Physiological; Pregnancy; Premature Infant; Principal Component Analysis; Productivity; Prospective, cohort study; Proteobacteria; Research; Research Personnel; Risk; Sample Size; Shotguns; Signal Transduction; Stomach; System; Taxonomy; Testing; Time; Training; Validation; Very Low Birth Weight Infant; Volatile Fatty Acids; Work; age related; biomarker development; biomarker validation; career development; cell motility; commensal bacteria; commensal microbes; evidence base; feeding; gastrointestinal; gut microbiome; gut microbiota; high throughput analysis; improved outcome; innovation; metabolomics; microbiome; microbiota; microbiota metabolites; motility disorder; multidisciplinary; novel; nutrition; operation; patient population; perinatal medicine; predictive modeling; prevent; programs; prospective; recruit; segregation; skills; skills training; stool sample; tool; translational medicine

1 Eric B. Ortigoza, MD, MSCR is a Neonatal-Perinatal Medicine physician with a Master of Science in Clinical 2 Research at UT Southwestern Medical Center (UTSW). His goal is to be an independently funded investigator 3 with expertise in neonatal gastrointestinal motility. He plans to investigate novel, comprehensive objective 4 methods to differentiate developmental feeding intolerance (DFI) from pathologic feeding intolerance (PFI) with 5 the goal of limiting unnecessary feeding delays, parenteral nutrition, and improving outcomes in preterm infants. 6 In a prospective, longitudinal cohort study, preterm infants who are born <32 weeks’ gestation will undergo 7 weekly non-invasive electrogastrography (EGG), abdominal near-infrared spectroscopy (aNIRS), and stool 8 collection. Dr. Ortigoza’s specific aims are to 1) quantify postmenstrual age-dependent differences in non- 9 invasive continuous gastrointestinal monitoring in preterm infants with DFI, PFI, and no feeding intolerance (NFI), 10 and 2) measure postmenstrual age-dependent differences in the gut microbiome and microbiota-derived 11 metabolites in preterm infants with DFI, PFI, and NFI. Dr. Ortigoza’s innovative approach integrates objective 12 gastrointestinal biomarkers of gastric motility, mesenteric oxygenation, bacterial colonization, and microbiota- 13 derived metabolites to differentiate DFI from PFI. The ability to differentiate between the two conditions will 14 encourage the development of predictive models for PFI in preterm infants using bioinformatics and machine 15 learning. The ability to predict PFI will help develop evidence-based strategies aimed at preventing and/or 16 treating episodes of PFI. Dr. Ortigoza has assembled a multidisciplinary team of mentors with expertise in the 17 key areas of computational modeling of complex physiological variables (Lina Chalak, MD, MSCS), advanced 18 gut microbiome profiling (Andrew Koh, MD and Julie Mirpuri, MD), and metabolite analysis (Andrew Koh, MD). 19 UTSW and its strong clinical research operation provide the ideal environment to conduct the proposed studies 20 with the large patient population at Parkland Health and Hospital System (PHHS) and Children’s Health, a 21 dedicated Center for Translational Medicine, and a strong record of clinical research participation. Dr. Ortigoza’s 22 Career Development Plan includes a comprehensive focused strategy to address the specific key training skills 23 that will allow him to transition to independence including: 1) developing expertise in complex signal analysis of 24 EGG and aNIRS data, 2) gaining expertise in interpretation of high throughput analysis of the gut microbiome 25 and its derived metabolites, and 3) developing expertise in biomarker development/validation. In addition, he will 26 receive training to develop leadership skills that are critical to fostering a productive research team and building 27 a successful research program. Together with his scientific aims, these goals will provide the skills necessary 28 for Dr. Ortigoza to build his independent research program in neonatal gastrointestinal motility.

Eric B.Ortigoza，医学博士，MSCR是一名新生儿-围产期内科医生，拥有临床理学硕士学位 2在德克萨斯大学西南医学中心(UTSW)研究。他的目标是成为一名独立资助的调查员 3具有新生儿胃肠动力方面的专业知识。他计划调查新的、全面的目标 4区分发育性和病理性喂养不耐受的方法 5减少不必要的喂养延迟、肠外营养和改善早产儿结局的目标。 6在一项前瞻性的纵向队列研究中，怀孕32周的早产儿将接受 每周7次无创胃电(EGG)、腹部近红外光谱(ANIRS)和大便检查 8个收藏。Ortigoza博士的具体目标是1)量化非月经后年龄相关性差异 9有DFI、PFI和无喂养不耐受(NFI)早产儿的有创持续胃肠监测， 10和2)测量绝经后肠道微生物组和微生物区系随年龄变化的差异 DFI、PFI和NFI早产儿的11种代谢物Ortigoza博士的创新方法将目标 胃动力、肠系膜氧合、细菌定植和微生物区系的12项胃肠生物标志物- 13种代谢产物用于区分DFI和PFI。区分这两种情况的能力将 14鼓励利用生物信息学和机器技术开发早产儿PFI的预测模型 15学习。预测PFI的能力将有助于制定旨在预防和/或 16次PFI治疗。Ortigoza博士组建了一支由多学科导师组成的团队，他们在 复杂生理变量计算建模的17个关键领域(Lina Chalak、MD、MSCs)，高级 18肠道微生物组分析(Andrew Koh，MD和Julie Mirpui，MD)和代谢物分析(Andrew Koh，MD)。 19 UTSW及其强大的临床研究业务为开展拟议研究提供了理想的环境 20由于帕克兰卫生和医院系统(PHHS)和儿童健康中心的患者人数众多， 21致力于转化医学中心，并有良好的临床研究参与记录。奥尔蒂戈萨医生的 22职业发展计划包括一个全面的重点战略，以解决具体的关键培训技能 23这将使他能够过渡到独立，包括：1)开发复杂信号分析方面的专业知识 24个鸡蛋和近红外光谱数据，2)在解释肠道微生物组的高通量分析方面获得专业知识 25及其衍生代谢物，以及3)开发生物标记物开发/验证方面的专门知识。此外，他还将 26接受培训以发展领导技能，这些技能对于培养富有成效的研究团队和建设 27一个成功的研究项目。与他的科学目标一起，这些目标将提供必要的技能 28为奥尔蒂戈扎博士建立他在新生儿胃肠动力方面的独立研究项目。