Early life protein-enriched human milk diets to increase lean body mass accretion and diversity of the gut microbiome in extremely preterm infants: a randomized trial

摘要 这个以患者为导向的导师研究职业发展奖(K23)的目的是为Ariel提供 答：Salas，医学博士，MSPH，拥有成为 独立的临床科学家和新生儿营养研究的领导者。他的长期职业目标是减少 通过新的翻译研究和大规模、多中心临床研究了解出生后发育障碍的负担 有希望的饮食干预措施的试验，这些干预措施优化生长，减少肠道微生物群的失调，以及 最终改善神经发育。他的直接目标是获得进行临床研究所需的技能。 研究蛋白质摄入量和肠道微生物群对生长和身体影响的研究计划 极早产儿(妊娠28周或以下)的构成。为了实现这些目标和过渡 为了独立，萨拉斯博士和他的导师们发展了全面的研究和职业生涯 发展计划，包括来自一支杰出的科学家团队的指导，该团队拥有经过证明的 成功的指导；密集的教学培训；以及有目的地设计的研究计划，以提供 体验式学习在研究出生后发育障碍和肠道微生物群中的高级研究方法 极早产儿的症状。在近26,000人中，约有60%的人发生了出生后生长障碍 美国每年都有极早产儿出生。出生后发育迟缓与 不良健康结局的风险更高，特别是当脂肪质量(FM)的增加高于脱脂质量时 (FFM)收益。萨拉斯博士最近的研究表明，极早产儿不能耐受早产 出生后头两周内的肠道喂养量进展增加了中断的风险 肠道微生物群的成熟和出生后生长障碍的风险增加。在研究计划中 在这份K23提案中概述的，Salas博士将通过1)研究早期的影响来扩展这项工作 出生后富含生命蛋白的饮食对极早产儿FFM积累的影响和2)成熟鉴定 区分早产儿出生后发育障碍和FFM减少的肠道微生物群模式 来自出生后生长正常且FFM沉积正常的早产儿。这项工作将 为早产儿出生后发育障碍的发病机制提供了新的见解，并将作为 Salas博士的基金会，以告知他未来的R01建议，并发现新的、基于证据的方法 预防出生后发育障碍。他的职业发展计划勾勒出了一条清晰的获取知识的途径， 成为一名独立的新生儿临床医生科学家、领导者和创新者所需的技能和经验 营养学研究。

SUMMARY The purpose of this Mentored Patient-Oriented Research Career Development Award (K23) is to provide Ariel A. Salas, MD, MSPH, with the mentorship, training, and research experience needed to become an independent clinician scientist and leader in neonatal nutrition research. His long-term career goal is to reduce the burden of postnatal growth failure through novel translational studies and large scale, multi-center clinical trials of promising dietary interventions that optimize growth, reduce dysbiosis of the gut microbiome, and ultimately improve neurodevelopment. His immediate goal is to acquire the skills needed to conduct a clinical research program to study the effects of the protein intake and gut microbiome on growth and body composition of extremely preterm infants (28 weeks of gestation or less). To achieve these goals and transition to independence, Dr. Salas and his mentors have developed a comprehensive research and career development plan that includes mentorship from an exceptional team of scientists with proven track records of successful mentorship; intensive didactic training; and a research plan that is purposefully designed to provide experiential learning in advanced research methods to study postnatal growth failure and the gut microbiome of extremely preterm infants. Postnatal growth failure occurs in approximately 60% of the nearly 26,000 extremely preterm infants born every year in the United States. Postnatal growth failure is associated with a higher risk of adverse health outcomes, particularly when fat mass (FM) gains are higher than fat-free mass (FFM) gains. Recent work by Dr. Salas suggests that extremely preterm infants unable to tolerate early progression of enteral feeding volumes during the first 2 weeks after birth have an increased risk of disrupted maturation of the gut microbiome and an increased risk of postnatal growth failure. In the research plan outlined in this K23 proposal, Dr. Salas will expand upon this work by 1) investigating the effects of early postnatal life protein-enriched diets on FFM accretion in extremely preterm infants and 2) identifying maturation patterns of the gut microbiome that differentiate preterm infants with postnatal growth failure and reduced FFM accretion from preterm infants with appropriate postnatal growth and normal FFM accretion. This work will produce novel insights into the pathogenesis of postnatal growth failure in preterm infants and will serve as the foundation for Dr. Salas to inform his future R01 proposals and discover new, evidence-based approaches to prevent postnatal growth failure. His career development plan outlines a clear path to gain the knowledge, skills, and experience needed to become an independent clinician scientist, leader, and innovator in neonatal nutrition research.