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: 9135637
• 负责人: HUICHUAN J LAI
• 金额: $ 15.04万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-20 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9135637
• 关键词: 20 year old; 6 year old; Affect; Age; American; Antibiotics; Attenuated; Benefits and Risks; Blood; Boston; Breast Feeding; Calories; Cessation of life; Child; Cities; Clinical; Clinical Data; Clinical Research; Country; Cystic Fibrosis; Data; Data Collection; Diagnosis; Diet; Early Diagnosis; Enrollment; Epidemiologic Studies; Essential Fatty Acids; European; Exclusive Breastfeeding; Exocrine pancreatic insufficiency; Fatty Acids; Feeding Methods; Food; Foundations; Frequencies; Funding; Genetic; Genotype; Grant; Growth; Guidelines; Health; Hereditary Disease; Human Milk; Immunologics; Infant; Infant Care; Infection; Intake; Knowledge; Lead; 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; Property; Proteins; Proton Pump Inhibitors; Pseudomonas; Pseudomonas Infections; Pseudomonas aeruginosa; Pulmonary Cystic Fibrosis; Pulmonary function tests; Records; Recurrence; Research; Research Project Grants; Respiratory Tract Infections; Respiratory physiology; Retrospective Studies; Role; Sampling; Severities; Siblings; Sodium; Sodium Chloride; Specimen; Supplementation; Symptoms; Testing; Thoracic Radiography; United States National Institutes of Health; Variant; Weaning; Weight Gain; children with cystic fibrosis; clinical care; cohort; cystic fibrosis patients; design; early childhood; evidence based guidelines; experience; feeding; follow-up; gut microbiota; improved; innovation; microbial; microbiome; prospective; rRNA Genes; sex; trend

 DESCRIPTION (provided by applicant): 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 160 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 during age 2-6 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, NBS 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.

 描述（由申请人提供）：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，即使是通过新生儿筛查早期诊断出来的婴儿也是如此。阻塞性肺病伴反复呼吸道感染是不可避免的。 2008年，中位生存年龄已提高至38岁，但仍有20%的死亡发生在20岁之前。 这笔赠款的总体目标是评估纯母乳喂养和学前饮食对 CF 儿童在生命最初 6 年内的生长、营养状况和肺部健康的影响，并确定这些影响是否与母乳中必需脂肪酸摄入不足和肠道微生物群的变化有关。这将通过扩大自 2012 年以来在 4 个州（UT、WI、IN 和 MA）的 5 个 CF 中心网络中进行的高效、强大的多中心前瞻性观察研究（称为 FIRSTage0-2 研究）的后续行动来完成。 具体目标是：1) 调查 160 名 2 至 6 岁 CF 儿童纯母乳喂养 (exBF) 的潜在益处和风险（称为 FIRSTage2-6 研究），并检验以下假设：a) exBF 在生命最初 2 年内的抗假单胞菌感染益处导致 6 岁时肺功能更好，b) exBF 的早期生长迟缓效应在 6 岁时降低 强化母乳并丰富 2-6 岁的学龄前饮食； 2) 检验以下假设：母乳必需脂肪酸浓度低是由于母亲摄入量低造成的，使患有 CF 的 exBF 婴儿容易缺乏必需脂肪酸，并导致生长不良（母乳研究）； 3) 使用 16S rRNA 基因测序来表征粪便微生物群，并测试以下假设：a) 母乳喂养和配方奶喂养的 CF 婴儿的肠道微生物群存在差异，并且与抗生素暴露和质子泵抑制剂的使用频率有关，b) 肠道微生物群的差异与生长/营养状况不佳和肺部疾病的严重程度有关（肠道微生物组） 学习）。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，CF 的 NBS 在美国以及许多欧洲国家已普及。然而，对于早期诊断出的 CF 婴儿群体，最佳喂养方式尚不清楚。目标 #1 将确定纯母乳喂养是否确实是许多 CF 临床医生认为的喂养 CF 婴儿的首选方法。目标 2 将阐明 CF 中母亲饮食、母乳脂肪酸含量和婴儿必需脂肪酸状态之间的联系，为解决 CF 婴儿必需脂肪酸补充的长期争议提供所需的证据。利用目标 1 和目标 2 生成的大量临床数据，目标 3 不仅将增进我们对 CF 肠道微生物组的理解，而且将描述其对 CF 临床结果的影响。实现这笔赠款的目标将为患有囊性纤维化的婴儿的护理带来创新性的变化。