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 ...