Effects of human milk handling practices on peptide release and bioactivity in the preterm infant intestine

母乳处理方法对早产儿肠道肽释放和生物活性的影响

• 批准号: 10367622
• 负责人: David Charles Dallas
• 金额: $ 63.52万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-20 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10367622
• 关键词: Address; Affect; Anti-Bacterial Agents; Childhood; Data; Databases; Development; Digestion; Enterocytes; Exposure to; Freezing; Gastrointestinal tract structure; Goals; Growth; Growth and Development function; Health Promotion; Human Milk; In Vitro; Infant; Intestinal Content; Intestines; Knowledge; Mass Spectrum Analysis; Milk; Milk Proteins; Mission; Mothers; National Institute of Child Health and Human Development; Neonatal Intensive Care; Neonatal Intensive Care Units; Peptide Hydrolases; Peptides; Premature Infant; Proteins; Public Health; Research; Research Priority; Research Project Grants; Role; Sampling; Source; Structure; Supplementation; Techniques; Testing; antimicrobial; base; donor milk; feeding; fortification; gut health; immunoregulation; improved; in vitro activity; in vivo; innovation; macrophage; nutrition; pasteurization; preterm newborn; sample collection

Preterm infants in the NICU are fed human milk from their own mothers or donors, and exposed to a variety of handling practices, including fresh mother’s milk, frozen and thawed mother’s milk and Holder pasteurized donor milk. Freeze-thaw cycles and pasteurization can alter the structure of milk proteases and proteins, and these alterations can affect the release of milk peptides. Milk peptides present in the infant intestine have an array of activities including antimicrobial, and enterocyte- and macrophage-immunomodulatory. Differences in milk sources, processing, and storage may yield differential release of bioactive peptides, and therefore differential activities in the gastrointestinal tract of infants. There is a critical need to evaluate effects of milk handling practices on release of peptides within the infant and their bioactivities. Our long-term goal is to determine feeding practices for preterm infants that promote optimal ex utero development and growth. The overall objective of this proposal is to identify how common milk handling practices affect the release of gut health-promoting peptides within the preterm infant intestine. Our central hypothesis is that the identity and amounts of milk peptides released within the intestine of preterm infants fed with these milks will be markedly different and therefore will have different profiles of antimicrobial, and enterocyte- and macrophage-immunomodulatory actions. Our specific aims are to determine the 1) antimicrobial and bifidogenic activities, 2) enterocyte-immunomodulatory activity, and 3) macrophage- immunomodulatory activity of peptides in the intestinal contents of preterm infants fed fresh mother’s milk (MM), frozen and thawed mother’s milk (FTMM), Holder-pasteurized mother’s milk (HPMM) and Holder- pasteurized donor milk (HPDM). Our approach will be to collect intestinal samples from preterm neonates within the neonatal intensive care unit (NICU) after feeding milk exposed to different handling practices, extract the peptide component from these samples, test their antibacterial, bifidogenic and enterocyte- and macrophage-immunomodulatory activity in vitro, and identify the peptides via mass spectrometry and database searching techniques. This research is innovative because it identifies the bioactivities of peptides released during in vivo intestinal digestion and examines the effect of human milk handling practices. At the conclusion of this project, we expect to have determined 1) the extent to which milk peptides released in the preterm infant intestine express gut health-related bioactivity; and 2) how different milk handling practices affect peptide release and bioactivity. The positive impact of this research is that it will help determine optimal milk handling practices for preterm infants, and possibly supplementation strategies for milk that will lead to improved bioactivity within the infant gut.

新生儿重症监护病房 (NICU) 中的早产儿用自己的母亲或捐赠者的母乳喂养，并接受各种处理方法，包括新鲜母乳、冷冻和解冻母乳以及 Holder 巴氏灭菌的捐赠母乳。冻融循环和巴氏灭菌可以改变牛奶蛋白酶和蛋白质的结构，这些改变可以影响牛奶肽的释放。婴儿肠道中存在的乳肽具有一系列活性，包括抗菌、肠细胞和巨噬细胞免疫调节。奶源、加工和储存的差异可能会导致生物活性肽的释放不同，从而导致婴儿胃肠道中的活性不同。迫切需要评估牛奶处理方法对婴儿体内肽释放及其生物活性的影响。我们的长期目标是确定早产儿的喂养方式，以促进最佳的宫外发育和生长。该提案的总体目标是确定常见的牛奶处理方法如何影响早产儿肠道内促进肠道健康的肽的释放。我们的中心假设是，用这些牛奶喂养的早产儿肠道内释放的乳肽的特性和数量将明显不同，因此将具有不同的抗菌、肠细胞和巨噬细胞免疫调节作用。我们的具体目标是确定喂养新鲜母乳 (MM)、冷冻和解冻母乳 (FTMM)、Holder 巴氏灭菌母乳 (HPMM) 和 Holder-巴氏灭菌母乳 (HPMM) 的早产儿肠道内容物中肽的 1) 抗菌和双歧活性，2) 肠细胞免疫调节活性，3) 巨噬细胞免疫调节活性。 巴氏灭菌捐赠母乳 (HPDM)。我们的方法是在新生儿重症监护病房（NICU）内收集经过不同处理方法喂养的早产儿的肠道样本，从这些样本中提取肽成分，在体外测试其抗菌、双歧杆菌以及肠细胞和巨噬细胞免疫调节活性，并通过质谱和数据库搜索技术鉴定肽。这项研究具有创新性，因为它确定了体内肠道消化过程中释放的肽的生物活性，并检查了母乳处理实践的效果。在该项目结束时，我们希望确定：1）早产儿肠道中释放的乳肽表达肠道健康相关生物活性的程度； 2) 不同的牛奶处理方法如何影响肽的释放和生物活性。这项研究的积极影响在于，它将有助于确定早产儿的最佳牛奶处理方法，以及可能的牛奶补充策略，从而改善婴儿肠道内的生物活性。