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

项目摘要/摘要 囊性纤维化是最常见的缩短生命的遗传性疾病之一。它的特点是 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迟缓 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，中位存活年龄已提高到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龄前饮食的效果。 儿童出生前6年的生长发育、营养状况及肺健康的研究 确定这些影响是否与母乳中必需脂肪酸摄入量不足有关 肠道微生物区系的变异。这将通过扩大后续高效、强大的 多中心前瞻性观察性研究在4个州(UT， Wi、IN和MA)，自2012年以来，称为FIRSTage0-2研究。 具体目标是：1)调查纯母乳喂养(ExBF)的潜在好处和风险 2-6岁的儿童CF(称为FIRSTage2-6研究)，并检验假设a) 出生前两年exBF抗假单胞菌感染的益处导致6岁时肺功能较好 年和b)exBF的早期生长停滞效应在6年内通过强化母乳和 在6岁之前丰富学龄前儿童的饮食；2)检验低必需脂肪酸 母乳浓度过高是由于母亲摄入量较低，使患有CFF的BF婴儿容易患上必需的 脂肪酸缺乏，并导致生长不良(母乳研究)；3)描述粪便微生物区系 使用16S rRNA基因测序和检验假设a)肠道微生物区系不同于 母乳喂养和配方奶喂养的CF婴儿，与抗生素的暴露和使用频率有关 质子泵抑制剂，以及b)肠道微生物区系的差异与生长/营养状况差和 肺部疾病的严重程度(肠道微生物组研究)。 这项赠款中提出的研究是及时和非常有意义的，因为截至2010年，新生儿筛查 因为CF在美国和许多欧洲国家都很普遍。然而，最佳饲喂是未知的。 在这一极早期被诊断为CF婴儿的人群中。目标1将确定纯母乳喂养是否 事实上，许多CF临床医生认为，用CF喂养婴儿是首选的方法。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，产生必要的证据来解决长期存在的必需脂肪酸的争议 CF型婴儿的补充剂。利用目标1和目标2产生的丰富临床数据，目标3将 不仅加深了我们对CF肠道微生物群的了解，而且描述了它对临床预后的影响 参见实现这笔赠款的目标将导致对患有CF的婴儿的护理发生创新性的变化。

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.