Genetics and genomics of human breast milk composition

人类母乳成分的遗传学和基因组学

• 批准号: 10642841
• 负责人: KELSEY ELIZABETH JOHNSON
• 金额: $ 2.64万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10642841
• 关键词: Adult; Antibodies; Biological; Biological Assay; Biological Testing; Biology; Biopsy; Body mass index; Breast Feeding; Cells; Cellular biology; Characteristics; Child; Childhood; Circulation; Clinical; Colostrum; Communities; Community Health; Computational Biology; Core Facility; Data; Development; Epidemiologic Methods; Epidemiology; Epithelial Cells; Exclusive Breastfeeding; Factor Analysis; Fatty Acids; Foundations; Future; Gene Expression; Genes; Genetic; Genetic Determinism; Genomic DNA; Genomic approach; Genomics; Genotype; Growth; Growth Factor; Health; Health Benefit; Human; Human Milk; Human Subject Research; Immune; Immune system; Individual; Infant; Infant Health; Institution; Interdisciplinary Study; Intervention; Knowledge; Lactation; Leukocytes; Life; Link; Mammary gland; Maps; Maternal Health; Metabolic; Milk; Minnesota; Modification; Molecular; Molecular Analysis; Mothers; Multiomic Data; Nutritional status; Oligosaccharides; Outcome; Pathway interactions; Phenotype; Physiological; Play; Postpartum Period; Probiotics; Quantitative Trait Loci; RNA Sequences; Research; Resources; Role; Sampling; Shapes; Stains; System; Techniques; Testing; Time; Tissues; Training; Translational Research; Twin Cities; Universities; Variant; Woman; antimicrobial peptide; career; cell type; data integration; genetic epidemiology; genetic variant; genome-wide; host microbiome; improved; infant gut microbiome; maternal obesity; microbiome; milk microbiome; milk production; multiple omics; neonate; novel; nutrition; responsible research conduct; single-cell RNA sequencing; skill acquisition; tool

Project Summary Breastfeeding plays a critical role in infant and maternal health; however, the components of milk underlying the health effects of milk and consequences of variation in milk composition are not well understood. Except for a few milk components, the role of maternal genetics in milk composition is largely unknown, limiting the epidemiological tools available to tease apart the effects of variation in milk composition on infant and maternal health. Thus, enhancing our understanding of the genetic and genomic basis of variation in milk composition is critical for identifying the mechanisms linking breastfeeding to infant and maternal health outcomes. One such outcome is the infant gut microbiome, for which breastfeeding is a primary determinant, with implications for the nascent immune system and the child’s long-term metabolic health. This proposal contains a comprehensive analysis of the molecular and cellular composition of breast milk, the effect of maternal genetics on this composition, and the impact of host-microbiome interactions in milk on the infant gut microbiome. The results will provide foundational data for advancing milk research and help advance our knowledge of human nutrition during the critical first 1000 days of life. Three specific aims will address these priorities by (1) applying single cell RNA-seq to assess the cellular composition of milk at two time points in lactation, thus profiling changes in gene expression in the mammary gland across lactation and the maternal immune cells that provide critical immune support to the neonate; (2) identifying genetic variants associated with gene expression in milk (eQTLs) and cell type-eQTL interactions in milk; and (3) applying multi-omic data integration to milk gene expression, the milk microbiome, and infant gut microbiome to uncover the biological pathways underlying shared variation across these systems, and to assess the impact of maternal metabolic health on these pathways. Each Aim will leverage cutting edge genomics techniques never previously applied to human milk to expand our understanding of the genetic and genomic basis of milk composition. Research will take place at the University of Minnesota – Twin Cities, a major research institution, with state-of-the-art core facilities for genomics and clinical/translational research. The trainee will receive training in the biology of milk and lactation, computational biology, human subjects research, and responsible conduct of research from an interdisciplinary sponsorship team in the departments of Epidemiology & Community Health and Genetics, Cell Biology and Development. This training plan will result in the trainee acquiring the skills and a scientific foundation to launch her independent academic career.

项目概要 母乳喂养对婴儿和孕产妇健康起着至关重要的作用；然而，牛奶的基本成分 牛奶对健康的影响以及牛奶成分变化的后果尚不清楚。除了 由于母乳成分中的一些成分，母体遗传在乳成分中的作用在很大程度上是未知的，限制了 流行病学工具可用于区分牛奶成分变化对婴儿和母亲的影响 健康。因此，增强我们对牛奶成分变异的遗传和基因组基础的理解是 对于确定母乳喂养与婴儿和孕产妇健康结果之间的联系机制至关重要。这样的一位 结果是婴儿肠道微生物群，母乳喂养是其主要决定因素，对 新生的免疫系统和孩子的长期代谢健康。该提案包含一个 综合分析母乳的分子和细胞成分，对母乳的影响 这种成分的遗传学，以及牛奶中宿主-微生物组相互作用对婴儿肠道的影响 微生物组。研究结果将为推进牛奶研究提供基础数据，并有助于推进我们的研究 生命中关键的前 1000 天的人类营养知识。三个具体目标将解决这些问题 优先事项：(1) 应用单细胞 RNA-seq 评估牛奶中两个时间点的细胞组成 哺乳期，从而分析哺乳期和母体乳腺基因表达的变化 为新生儿提供关键免疫支持的免疫细胞； (2) 识别相关的遗传变异 牛奶中的基因表达 (eQTL) 以及牛奶中的细胞类型-eQTL 相互作用； (3) 应用多组学数据 整合乳汁基因表达、乳汁微生物组和婴儿肠道微生物组，以揭示生物学 这些系统之间存在共同变异的途径，并评估母体代谢的影响 这些途径上的健康。每个目标都将利用以前从未应用过的尖端基因组学技术 研究母乳，以扩大我们对乳汁成分的遗传和基因组基础的了解。研究 将在明尼苏达大学双城分校举行，该大学是一个重要的研究机构，拥有最先进的技术 基因组学和临床/转化研究的核心设施。受训者将接受生物学培训 牛奶和哺乳、计算生物学、人类受试者研究以及负责任的研究行为 流行病学、社区健康和遗传学系的跨学科赞助团队， 细胞生物学和发育。该培训计划将使受训者获得技能和科学的知识 基金会开始她的独立学术生涯。