Mammary Epithelium Permeability, Lactation Outcomes, and Infant Health

项目总结/摘要 人乳为婴儿提供了显著的健康益处。除了营养成分，母乳还含有抗体， 免疫力，与肠道上皮成熟相关的生长因子，用于建立肠道的细菌 微生物组和调节炎症的代谢物。母乳中的这些重要元素 婴儿肠道内免疫系统的强大发展和更好的婴儿健康。不幸的是，许多父母 计划母乳喂养的婴儿会比计划的更早补充或断奶，并经常报告感觉到母乳不足。 供应是原因。乳腺上皮渗透性（IMEP）增加，如乳汁升高所示 钠是一种生理条件，可能对乳汁分泌、组成 婴儿保健。哺乳生理学研究已经确定，封闭的细胞旁途径，即，低 渗透性，是建立和维持足够的乳汁分泌所必需的。人类研究 对渗透性的研究主要集中在分泌激活期和持久性乳腺上皮 产后第7天的渗透性与感觉到的低乳汁供应有关。然而， 在确定的哺乳期内的IMEP。我们最近报道，美国女性中的IMEP更常见 比以前认识到的要多。需要纵向US研究来量化乳腺癌 上皮渗透性在建立哺乳期，并调查在何种程度上增加 渗透性影响泌乳不足。我们的总体目标是建立一个临床相关的稳健的 IMEP阈值，基于我们对钠作为连续变量的分析，并确定 IMEP与次优泌乳结果和婴儿健康下降有关。我们提出 IMEP与低乳供应和早于期望的断奶有关。我们还证实了IMEP结果 改变牛奶营养成分，改变炎症特征和牛奶微生物组组成， 婴儿肠道免疫特征和微生物组。我们将招募一个来自纽约的400对母婴配对的多元化队列， 墨西哥和马萨诸塞州。参与者将在四个时间点提供双侧乳汁和婴儿粪便样本 包括过渡期、早期和成熟乳。了解IMEP与次优泌乳的联系程度 结果和婴儿肠道健康是非常重要的，因为IMEP可以测量，治疗和 防止。限制IMEP的干预措施可能包括行为和饮食改变，以及药物治疗或 补充剂.这将是第一项确定IMEP患病率和牛奶相关变化的研究 在产后的前五个月，也是唯一一项关于IMEP的大型美国队列研究。结果从这个 这项研究可能会导致临床实践的重大变化。牛奶中IMEP的评估可能成为常规， 特别是在寻求哺乳咨询的妇女中，这可能会改善结果。我们预计 我们的地理和种族多样化的队列将提供关于风险因素差异的新数据， IMEP与泌乳结果的关系。

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.