Early Childhood Diet, Growth, Gut Microbiome And Lung Health in Cystic Fibrosis

囊性纤维化中的幼儿饮食、生长、肠道微生物组和肺部健康

• 批准号: 10017175
• 负责人: HUICHUAN J LAI
• 金额: $ 66.55万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10017175
• 关键词: 16S ribosomal RNA sequencing; 20 year old; 3 year old; 6 year old; Affect; Age; American; Antibiotics; Attenuated; Benefits and Risks; Biological Markers; Birth; Blood; Boston; Breast Feeding; Breastfed infant; Calories; Caring; Cessation of life; Child; Cities; Clinical; Clinical Data; Clinical Research; Country; Cystic Fibrosis; Data; Data Collection; Diagnosis; Diet; Early Diagnosis; Enrollment; Essential Fatty Acids; European; Exclusive Breastfeeding; Exocrine pancreatic insufficiency; Fatty Acids; Feeding Methods; Food; Formula supplementation; Foundations; Frequencies; Funding; Future; Genetic Diseases; Genotype; Goals; Grant; Growth; Guidelines; Health; Human Milk; Immunologics; Infant; Infant Care; Infection; Intake; Knowledge; Lactation; Life; Link; Linoleic Acids; Lung; Lung diseases; Malnutrition; Medical; Mothers; Multicenter Studies; Neonatal Screening; Nursery Schools; Nutrient; Nutritional; Nutritional status; Observational Study; Obstructive Lung Diseases; Outcome; Pancreas; Patients; Pharmaceutical Preparations; Population; Population trends; Property; Proteins; Proton Pump Inhibitors; Pseudomonas; Pseudomonas Infections; Pseudomonas aeruginosa; Pseudomonas aeruginosa infection; Pulmonary function tests; Records; Recurrence; Research; Research Project Grants; Respiratory Signs and Symptoms; Respiratory Tract Infections; Respiratory physiology; Retrospective Studies; Role; Sampling; Severities; Siblings; Sodium; Sodium Chloride; Specimen; Testing; Thoracic Radiography; Time; United States National Institutes of Health; Variant; Weight Gain; children with cystic fibrosis; cohort; cystic fibrosis patients; design; early childhood; epidemiology study; evidence based guidelines; experience; fatty acid supplementation; fecal microbiome; fecal microbiota; feeding; follow-up; gut microbiome; gut microbiota; improved; infancy; innovation; microbial; microbiome research; mother nutrition; prospective; recruit; sex

PROJECT SUMMARY/ABSTRACT Cystic fibrosis (CF) is one of the most common life-shortening genetic diseases. It is characterized by pancreatic insufficiency, resulting in malnutrition and growth faltering even in infants diagnosed early through newborn screening. Obstructive lung disease with recurrent respiratory infections is inevitable. Median age of survival has improved to 38 years in 2008, but 20% of deaths still occur before age 20 years. The overall objective of this grant is to assess the effects of exclusive breastfeeding and preschool diet on growth, nutritional status and pulmonary health in CF children through the first 6 years of life and determine if these effects are related to an insufficient essential fatty acid intake from breast milk and variations in gut microbiota. This will be done by expanding the follow-up of a highly productive, strong multi-center prospective observational study being conducted in a network of 5 CF Centers in 4 states (UT, WI, IN and MA) since 2012, referred to as FIRSTage0-2 study. Specific Aims are: 1) to investigate the potential benefits and risks of exclusive breastfeeding (exBF) in children with CF from age 2 to 6 years (referred to as FIRSTage2-6 study) and test the hypotheses that a) the anti-pseudomonas infection benefit of exBF in the first 2 years of life results in better lung function at age 6 years and b) the early growth-faltering effect of exBF is reduced at 6 years by fortifying human milk and enriching the preschool diet through age 6 years; 2) to test the hypothesis that low essential fatty acid concentration of breast milk results from low maternal intake, predisposes exBF infants with CF to essential fatty acid deficiencies, and contributes to poor growth (Breast Milk study); 3) to characterize fecal microbiota using 16S rRNA gene sequencing and testing the hypotheses that a) the gut microbiota differs between breastfed and formula-fed CF infants and is related to the frequency of antibiotic exposure and use of proton pump inhibitor, and b) differences in gut microbiota are related to poor growth/nutritional status and the severity of lung disease (Gut Microbiome study). Research proposed in this grant is timely and highly significant, because as of 2010, newborn screening for CF is universal in the US as well as in many European countries. However, optimal feeding is unknown in this very early diagnosed population of CF infants. Aim #1 will determine if exclusive breastfeeding is indeed the preferred method of feeding infants with CF as perceived by many CF clinicians. Aim 2 will elucidate the links between maternal diet, breast milk fatty acid content and infant essential fatty acid status in CF, generating the needed evidence to resolve the long-standing controversy of essential fatty acid supplementation for CF infants. Utilizing the wealth of clinical data generated from Aims 1 and 2, Aim 3 will not only advance our understanding of gut microbiome in CF but delineate its impact on clinical outcomes of CF. Accomplishing the aims of this grant will lead to innovative changes in the care of infants with CF.

项目摘要/摘要 囊性纤维化（CF）是最常见的遗传疾病之一。它的特征是 胰腺功能不全，即使在早期诊断的婴儿中也会导致营养不良和生长步履蹒跚 通过新生儿筛查。具有复发性呼吸道感染的阻塞性肺疾病是不可避免的。 2008年，生存年龄的中位年龄已提高到38岁，但20％的死亡仍发生在20岁之前。 该赠款的总体目的是评估独家母乳喂养和学龄前饮食的影响 在生命的前6年，CF儿童的增长，营养状况和肺部健康 确定这些影响是否与母乳中的必需脂肪酸摄入不足有关，并且 肠道菌群的变化。这将通过扩展高生产力，强大的随访来完成 多中心的前瞻性观察性研究正在4个州的5 CF中心网络中进行（UT， 自2012年以来，WI，IN和MA）被称为Firstage0-2研究。 具体目的是：1）调查独家母乳喂养的潜在益处和风险（EXBF） CF从2至6岁到6岁的儿童（称为Firstage2-6研究），并测试假设a） EXBF在生命的头两年中的抗假单胞菌感染益处可在6岁时获得更好的肺功能 年和b）通过加固人牛奶和 通过6岁，丰富学龄前饮食； 2）检验低必需脂肪酸的假设 母乳的浓度是由低母体摄入量，易患CF的EXBF婴儿到必不可少的 脂肪酸缺乏症，导致生长不良（母乳研究）； 3）表征粪便菌群 使用16S rRNA基因测序并测试假设a）肠道微生物群不同 母乳喂养和配方奶的CF婴儿，与抗生素暴露的频率有关，并使用 质子泵抑制剂，b）肠道菌群的差异与生长/营养状况差有关 肺部疾病的严重程度（肠道微生物组研究）。 这笔赠款中提出的研究是及时且非常重要的，因为截至2010年，新生儿筛查 因为CF在美国以及许多欧洲国家都是普遍的。但是，最佳喂养尚不清楚 在这个早期诊断的CF婴儿中。 AIM＃1将确定独家母乳喂养是否为 确实，许多CF临床医生认为，用CF喂养婴儿的首选方法。 AIM 2意志 阐明孕产妇饮食，母乳脂肪酸含量和婴儿必需脂肪酸状态之间的联系 在CF中，生成所需的证据以解决必需脂肪酸的长期争议 补充CF婴儿。利用AIM 1和2产生的大量临床数据，AIM 3将 不仅可以促进我们对CF中肠道微生物组的理解，还描述了其对临床结果的影响 参见实现这笔赠款的目标将导致CF婴儿护理的创新变化。