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: 9321018
• 负责人: HUICHUAN J LAI
• 金额: $ 68.67万
• 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 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9321018
• 关键词: 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; Genotype; Goals; Grant; Growth; Guidelines; Health; Hereditary Disease; 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; Pulmonary function tests; Records; Recruitment Activity; Recurrence; Research; Research Project Grants; Respiratory Signs and Symptoms; Respiratory Tract Infections; Respiratory physiology; Retrospective Studies; Role; Sampling; Severities; Siblings; Sodium; Sodium Chloride; Specimen; Supplementation; 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; feeding; follow-up; gut microbiome; gut microbiota; improved; infancy; innovation; microbial; microbiome; microbiota; prospective; rRNA Genes; 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.

项目总结/摘要 囊性纤维化（CF）是最常见的缩短寿命的遗传性疾病之一。它的特点是 胰腺功能不全，导致营养不良和生长迟缓，即使在婴儿早期诊断 通过新生儿筛查。阻塞性肺病合并反复呼吸道感染是不可避免的。 2008年，中位生存年龄提高到38岁，但仍有20%的死亡发生在20岁之前。 这项补助金的总体目标是评估纯母乳喂养和学前饮食的影响 CF儿童在生命的前6年的生长、营养状况和肺部健康， 确定这些影响是否与母乳中必需脂肪酸摄入不足有关， 肠道微生物群的变化。这将通过扩大一个富有成效的、强有力的 多中心前瞻性观察性研究正在4个州（UT， WI、IN和MA），称为FIRSTage 0 -2研究。 具体目的是：1）调查纯母乳喂养（exBF）的潜在益处和风险， 2 - 6岁CF儿童（称为FIRSTage 2 -6研究），并检验以下假设：a） 出生后前2年exBF的抗假单胞菌感染获益导致6岁时肺功能更好 B）通过强化人乳在6年时降低了exBF的早期生长停滞效应， 丰富学龄前饮食，直到6岁; 2）测试低必需脂肪酸的假设， 母乳浓度的结果，从低母亲的摄入量，倾向于暴露BF婴儿CF的基本 脂肪酸缺乏，并导致生长不良（母乳研究）; 3）表征粪便微生物群 使用16 S rRNA基因测序并测试以下假设：a）肠道微生物群在以下方面不同： 母乳喂养和配方奶粉喂养的CF婴儿，并与抗生素暴露的频率和使用 质子泵抑制剂，和B）肠道微生物群的差异与不良生长/营养状态有关， 肺部疾病的严重程度（肠道微生物组研究）。 这项拨款中提出的研究是及时的，具有高度意义，因为截至2010年， CF在美国和许多欧洲国家都是通用的。然而，最佳喂养是未知的 在这个非常早期诊断的CF婴儿群体中。目标1将确定纯母乳喂养是否 事实上，这是许多CF临床医生认为的喂养CF婴儿的优选方法。目标2将 阐明母亲饮食、母乳脂肪酸含量和婴儿必需脂肪酸状况之间的联系 在CF中，产生所需的证据来解决长期存在的必需脂肪酸争议， CF婴儿的补充剂。利用目标1和2产生的丰富临床数据，目标3将 这不仅促进了我们对CF中肠道微生物组的理解， 参见实现这一赠款的目标将导致CF婴儿护理的创新变化。