Milk Analytics Core

摘要 加州圣地亚哥大学（UC San Diego）MPRINT治疗学卓越中心（CET） 涉及以母乳（HM）为中心的方法，以研究孕产妇和儿科治疗在 母亲-牛奶-婴儿“三元组”的交叉点。MPRINT CET的总体目标中的关键是评估 母体抗生素如何影响HM成分以及HM成分如何改变这些抗生素的安全性和有效性 重要的儿科治疗药物。然而，HM成分分析并不简单。HM成分高度 在整个哺乳期，甚至在一次喂养过程中，都是动态的和变化的。HM是一个 复杂的基质，包括细胞和微生物以及大分子聚集体，如乳脂球。 人乳还含有一组独特的分子，即人乳低聚糖（HMO）， 人乳中含量仅次于乳糖和脂质的成分。因此，HM的动态、复杂和独特的性质 需要特定的采集方案、检测开发和检测验证。拥有超过20年的经验 在母乳研究中，牛奶分析核心（MAC）将为MPRINT CET提供全面的指导和建议 调查员和工作人员。MAC将提供HM采集协议和准备装运的样本采集套件， 临床和数据科学项目（目标1a），并接收人乳样品进行成分分析（目标1b）。 根据项目需要，MAC还提供常量营养素、低聚糖和生物活性测量 作为牛奶微生物组分析，后者与加州大学圣地亚哥分校微生物组核心合作， 独立于我们的团队，但经常与我们的团队合作。MAC还将提供鼠乳低聚糖 和微生物组分析的研究项目团队（目标1c），应用我们详细的先验知识， 研究中的St 3gal 4突变显着减少唾液酸化乳低聚糖含量。生成的数据 我们的分析将返回给各自的项目团队进行整合。将HM等分试样与 相同的样本将直接传递给抗生素的药物计量学和分析化学核心 这些数据也将直接返回给各自的项目小组。除了 已经建立的服务，MAC将开发和验证新的HM特异性测定，通过扩大分析物 现有多重免疫分析平台（Aim 2a）的组合，并通过参与和激活其他UC San 迭戈研究人员将其独特的技术应用于HM研究并进行验证（目标2b）。我们设想MAC 成为一个拥有知识、技能和技术的综合牛奶分析核心， 这和其他MPRINT CET和整个生物医学研究界。团结起来，我们将能够 更好地了解怀孕和哺乳期间的抗生素治疗如何影响母亲- 母乳-婴儿“三合一”，告知和调整治疗的精确性，并最终改善母婴健康。

ABSTRACT The University of California San Diego (UC San Diego) MPRINT Center of Excellence in Therapeutics (CET) involves a human milk (HM)-centered approach to investigate the role of maternal and pediatric therapeutics at intersections of the mother-milk-infant ‘triad’. Key among the overall goals of the MPRINT CET are to assess how maternal antibiotics impact HM composition and how HM components alter safety and efficacy of these important pediatric therapeutic agents. HM composition analysis, however, is not trivial. HM composition is highly dynamic and changes throughout lactation, indeed even throughout the course of a single feeding. HM is a complex matrix that includes cells and microbes as well as large molecule aggregates like the milk fat globule. HM also contains a unique set of molecules, the human milk oligosaccharides (HMOs), which represent the third most abundant component of HM after lactose and lipids. Thus, the dynamic, complex, and unique nature of HM requires specific collection protocols, assay development, and assay validation. With over 20 years of experience in HM research, the Milk Analytics Core (MAC) will provide overall guidance and advice to MPRINT CET investigators and staff. MAC will provide HM collection protocols and ready-to-ship sample collection kits to the Clinical and Data Science Projects (Aim 1a) and receive HM samples for composition analysis (Aim 1b). Depending on project needs, MAC offers macronutrient, oligosaccharide, and bioactive measurements as well as milk microbiome analysis, the latter in collaboration with the UC San Diego Microbiome Core, which operates independently of, but frequently in partnership with, our team. MAC will also provide mouse milk oligosaccharide and microbiome analyses to the Research Project team (Aim 1c), applying our detailed prior knowledge of how the St3gal4 mutation under study markedly depletes sialylated milk oligosaccharide content. Data generated from our analyses will be returned to the respective project teams for integration. Separate HM aliquots from the same samples will be passed directly on to the Pharmacometrics and Analytical Chemistry Core for antibiotic drug quantification, and that data will likewise be directly returned to the respective project teams. In addition to already established services, MAC will develop and validate new HM-specific assays by expanding the analyte portfolio of the existing multiplex immunoassay platform (Aim 2a) and by engaging and activating other UC San Diego researchers to apply and validate their unique technologies to HM research (Aim 2b). We envision MAC to become a comprehensive milk analytics core with knowledge, skills, and technology, serving as a resource to this and other MPRINT CETs and the biomedical research community at large. Together, we will be able to generate a better understanding how antibiotic treatment during pregnancy and lactation impacts the mother- milk-infant ‘triad’, inform and adjust precision in therapeutics, and ultimately improve maternal-child health.