Necrotizing Enterocolitis: Prevention and Prediction

坏死性小肠结肠炎：预防和预测

• 批准号: 7933176
• 负责人: CARLITO B LEBRILLA
• 金额: $ 17万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7933176
• 关键词: Address; Bacteria; Bifidobacterium; Biochemical Genetics; Biological Assay; Biological Markers; Blinded; Breast Feeding; California; Clinical; Clinical Trials; Conduct Clinical Trials; Contracts; Copy Number Polymorphism; Cross-Over Studies; Data; Defensins; Development; Distal; Dose; Feces; Fermentation; Fiber; Foundations; Fucosidase; Future; Gene Dosage; General Population; Genes; Genetic; Genotype; Gestational Age; Growth; Health; Human Milk; In Vitro; Infant; Infection; Infection prevention; Integration Host Factors; Intervention; Intestines; Lead; Life; Meta-Analysis; Metagenomics; Microbe; Milk; Necrotizing Enterocolitis; Neuraminidase; Oligosaccharides; Organism; Pathogenesis; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Phase III Clinical Trials; Predisposition; Premature Infant; Premature Infant Diseases; Prevention; Preventive; Probiotics; Property; Relative (related person); Research; Risk; Saliva; Scientist; Series; Shapes; Supplementation; Testing; Tissues; Treatment Protocols; Umbilical Cord Blood; Universities; Urease; Urine; Work; antimicrobial peptide; bacterial genetics; base; bone; design; dietary supplements; feeding; high risk; high risk infant; improved; microbiome; microorganism; novel; pre-clinical; prebiotics; premature; prevent; protective effect; public health relevance; randomized placebo controlled trial; research study; tissue culture

DESCRIPTION (provided by applicant): Necrotizing enterocolitis (NEC) is a common and devastating disease of premature infants. Effective preventive agents and biomarkers predictive of high-risk infants are significant clinical needs. The most promising interventions shown to prevent NEC are breast milk feedings and probiotic microorganisms, although the mechanisms of action are unknown. Our proposal draws from the integrated, multi-disciplinary Milk Bioactives Consortium at the University of California Davis and includes exciting preliminary data: a clinical trial of two probiotic products in premature infants, evidence that human milk oligosaccharides selectively stimulate growth of specific bifidobacteria, and a novel potential biomarker of infant susceptibility. We hypothesize that a regimen of prebiotic oligosaccharides and/or probiotic microbes, which increases bifidobacteria colonization to mimic that of healthy term breast-fed infants, will improve infant growth and lead to an attractive regimen for larger trials of prevention of NEC. We further hypothesize that a low ¿-defensin gene copy number polymorphism predisposes some premature infants to development of an intestinal microbiota low in bifidobacteria and the consequent deficit in normal microflora protection increases their susceptibility to NEC. Specific Aim 1 will conduct Phase 1 and Phase 2 clinical trials to identify and evaluate a preferred dietary supplement regimen to achieve a predominance of bifidobacteria in the fecal microbiota of preterm infants. Specific Aim 2 will conduct a series of in vitro experiments to (a) analyze biochemical and genetic properties of the bifidobacteria in the feces of infants receiving prebiotic oligosaccharides and/or probiotic microbes and (b) analyze the prebiotic properties of components of human milk. Specific Aim 3 will analyze the potential of a novel genetic biomarker for susceptibility to NEC: ¿-defensin gene copy number. The proposed clinical trials and in vitro experiments are designed to answer important questions regarding the development of the intestinal microbiota, the effect of breast milk components on the developing intestinal microbiota, and the effect of changes in the intestinal microbiota on the health and growth of the premature infant. PUBLIC HEALTH RELEVANCE: Having more healthy bacteria in the intestines may improve growth and prevent infections in premature infants. By giving different doses and combinations of live healthy bacteria (probiotics) and fiber (prebiotics) to premature infants, we aim to find the best way to change the bacteria in the intestines to be more like those of healthy breast-fed term infants. The genes of premature infants who get intestinal infections may be slightly different from those who don't; we will test one group of particularly promising genes to see if that is true.

描述（由申请人提供）：坏死性小肠结肠炎 (NEC) 是早产儿的一种常见且毁灭性的疾病，有效的预防剂和预测高危婴儿的生物标志物是临床上最有希望的预防 NEC 的干预措施。和益生菌微生物，尽管作用机制尚不清楚，但我们的建议来自加州大学戴维斯分校的综合性多学科牛奶生物活性联盟，并包括令人兴奋的初步数据：一项临床试验。早产儿的两种益生菌产品，母乳寡糖选择性刺激特定双歧杆菌生长的证据，以及婴儿易感性的一种新的潜在生物标志物，我们发现益生元寡糖和/或益生菌微生物的养生法可以增加双歧杆菌的定植，以模仿双歧杆菌的定植。健康足月母乳喂养的婴儿，将改善婴儿生长，并为预防 NEC 的大型试验提供有吸引力的方案，我们进一步认为低 ¿ -防御素基因拷贝数多态性使一些早产儿的肠道微生物群的双歧杆菌含量较低，从而导致正常微生物群保护的缺陷增加了他们对 NEC 的易感性。 具体目标 1 将进行 1 期和 2 期临床试验，以识别和评估将实施优选的膳食补充剂方案，以实现早产儿粪便微生物群中双歧杆菌的优势。具体目标 3 将进行一系列体外实验，以 (a) 分析接受益生元寡糖和/或益生菌微生物的婴儿粪便中双歧杆菌的生化和遗传特性，以及 (b) 分析母乳成分的益生元特性。一种新的 NEC 易感性遗传生物标志物的潜力：¿ -防御素基因拷贝数。拟议的临床试验和体外实验旨在回答有关肠道微生物群发育、母乳成分对发育中肠道微生物群的影响以及肠道微生物群变化对肠道微生物群的影响等重要问题。早产儿的健康和成长：通过给予不同剂量和组合的活健康细菌（益生菌）和纤维，肠道内有更多的健康细菌可以改善早产儿的生长并预防感染。 （益生元）给早产儿，我们的目标是找到改变肠道细菌的最佳方法，使其更像健康母乳喂养的足月婴儿。 患有肠道感染的早产儿的基因可能与那些略有不同。不；我们将测试一组特别有前途的基因，看看这是否属实。