Mammary Epithelium Permeability, Lactation Outcomes, and Infant Health

乳腺上皮渗透性、哺乳结果和婴儿健康

• 批准号: 10753649
• 负责人: Kathleen Frances Arcaro
• 金额: $ 70.07万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-11 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10753649
• 关键词: 37 weeks gestation; Academy; Address; Affect; Allergic Disease; American; Anti-Inflammatory Agents; Antibodies; Antibody-mediated protection; Autoimmune Diseases; Bacteria; Behavioral; Bilateral; Birth; Black race; Breast; Breast Feeding; Carbohydrates; Cohort Studies; Counseling; Data; Dietary Intervention; Elements; Enrollment; Fatty acid glycerol esters; Geography; Goals; Growth; Growth Factor; Growth and Development function; Health; Health Benefit; Hispanic; Human; Human Milk; Immune; Immune system; Indigenous; Infant; Infant Health; Inflammation; Inflammatory; Intervention; Intestines; Knowledge; Lactation; Life; Link; Literature; Longitudinal Studies; Maintenance; Massachusetts; Measures; Milk; Mothers; New Mexico; Nutrient; Nutritional; Outcome; Parents; Participant; Pathway interactions; Pattern; Pediatrics; Perception; Periodicals; Permeability; Pharmaceutical Preparations; Physiological; Physiology; Population; Postpartum Period; Pregnant Women; Prevalence; Probiotics; Proteins; Public Hospitals; Questionnaires; Recommendation; Reporting; Research; Risk Factors; Role; Sampling; Severities; Sodium; Supplementation; Systems Development; Testing; Third Pregnancy Trimester; Tissues; United States; Weaning; Woman; Work; clinical practice; clinically relevant; cohort; cytokine; dietary; dysbiosis; ethnic diversity; gastrointestinal epithelium; gut microbiome; improved; improved outcome; infection risk; mammary; mammary epithelium; mastitis; microbial; microbiome; microbiome composition; milk microbiome; milk removal; milk secretion; milk supply; novel; obesity in children; prevent; racial diversity; recruit

Project Summary/Abstract Human milk provides significant health benefits for infants. Beyond nutrients, breastmilk contains antibodies for immunity, growth factors associated with gut epithelial maturation, bacteria for establishment of the gut microbiome, and metabolites that modulate inflammation. These important elements of human milk support strong immune system development within the infant gut and better infant health. Unfortunately, many parents aiming to breastfeed will supplement or wean earlier than planned and frequently report perceived low milk supply as the reason. Increased mammary epithelium permeability (IMEP), as indicated by elevated milk sodium, is a physiologic condition that could have significant implications for milk secretion, composition and infant health. Lactation physiology studies have established that closed paracellular pathways, i.e., low permeability, are essential for the establishment and maintenance of adequate milk secretion. Human studies on permeability have focused on the period of secretory activation and persistent mammary epithelium permeability at day 7 postpartum has been associated with perceived low milk supply. However, little is known about IMEP during established lactation. We recently reported that IMEP among US women is more common across lactation than previously recognized. Longitudinal US studies are needed to quantify mammary epithelium permeability during established lactation and to investigate the extent to which increased permeability influences lactation insufficiency. Our overall goal is to establish a clinically relevant robust IMEP threshold, based on our analysis of sodium as a continuous variable, and determine the extent to which IMEP is associated with suboptimal lactation outcomes and reduced infant health. We propose that IMEP is associated with low milk supply and earlier than desired weaning. We also posit that IMEP results in altered milk nutrient content, shifted inflammatory profiles and milk microbiome composition impacting the infant gut immune profile and microbiome. We will enroll a diverse cohort of 400 mother-infant dyads from New Mexico and Massachusetts. Participants will provide bilateral milk and infant fecal samples at four timepoints spanning transitional, early and mature milk. Understanding the extent of IMEP linkage to suboptimal lactation outcomes and infant intestinal health is of major importance because IMEP can be measured, treated and prevented. Interventions to limit IMEP could include behavioral and dietary changes, as well as medications or supplements. This will be the first study to determine the prevalence of IMEP and associated changes in milk throughout the first five months postpartum, and the only large US cohort study of IMEP. Results from this study could lead to a major change in clinical practice. Assessment of IMEP in milk could become routine, especially among women seeking lactation counseling, and this may lead to improved outcomes. We expect that our geographically and ethnically diverse cohorts will provide novel data on differences in risk factors for IMEP with implications for lactation outcomes.

项目摘要/摘要 人牛奶为婴儿提供了重大健康益处。除营养外，母乳还含有抗体 免疫力，与肠道上皮成熟相关的生长因子，肠道的细菌 调节炎症的微生物组和代谢产物。这些重要的人类牛奶支持元素 婴儿肠道内的强大免疫系统发展和更好的婴儿健康。不幸的是，许多父母 旨在母乳喂养会比计划的，并且经常报告低牛奶的乳房会补充或断奶 供应是原因。乳房上皮渗透率（IMEP）增加，如升高的牛奶所示 钠，是一种生理状况，可能对牛奶分泌，成分和 婴儿健康。哺乳生理研究已经确定，封闭细胞细胞途径，即低 渗透性对于建立和维持适当的牛奶分泌至关重要。人类研究 渗透性集中在分泌激活期和持续性乳腺上皮时期 在产后第7天的渗透性与感知到低牛奶供应有关。但是，鲜为人知 关于在既定的泌乳过程中的imep。我们最近报告说，imep中的女性更常见 在哺乳期比以前认识的。需要美国纵向研究来定量乳腺 在建立泌乳期间的上皮渗透性，并研究增加的程度 渗透性会影响泌乳不足。我们的总体目标是建立一个临床相关的鲁棒 imep阈值，基于我们对钠作为连续变量的分析，并确定 imep与次优泌乳结局和婴儿健康降低有关。我们建议 该IMEP与低牛奶供应相关，并且比所需的断奶早。我们还认为IMEP结果 在牛奶营养含量改变的情况下，炎症概况和牛奶微生物组成分影响 婴儿肠道免疫轮廓和微生物组。我们将招募新的400个来自新的母亲二元组的队列 墨西哥和马萨诸塞州。参与者将在四个时间点提供双边牛奶和婴儿粪便样品 跨越过渡，早期和成熟的牛奶。了解imep连接到次优泌乳的程度 结果和婴儿肠道健康至关重要，因为可以测量，治疗IMEP和 阻止。限制IMEP的干预措施可能包括行为和饮食变化，以及药物或 补品。这将是确定IMEP患病率和相关牛奶变化的第一项研究 在产后的前五个月中，这是IMEP的唯一大型美国队列研究。结果 研究可能导致临床实践的重大变化。评估牛奶中的IMEP可能会变得常规， 特别是在寻求哺乳咨询的妇女中，这可能导致进步的改善。我们期望 我们在地理和种族上多样化的人群将提供有关风险因素差异的新数据 IMEP对泌乳结果有影响。