Division of Neonatology and Division of Gastroenterology and Nutrition, Department of Pediatrics, Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research Excellence (MOMI CORE), University of California, La Jolla, California, USA,
Nestle Nutr Inst Workshop Ser. 2020;94:115-123. doi: 10.1159/000505339. Epub 2020 Mar 11.
Oligosaccharides are a group of complex glycans that are present in the milk of most mammals. However, human milk is unique as the concentrations of human milk oligosaccharides (HMOs) are much higher than those of other mammals, and their structural composition is more complex and varies between women. These observations prompt several questions: (i) Why are humans unique when it comes to milk oligosaccharides? (ii) Which maternal genetic and environmental factors drive the interindividual variation in HMO composition? (iii) What are the short- and long-term health benefits for the infant - and potentially also the mother? The combination of genome-wide association studies, milk transcriptomics, in vitro gene editing, and in silico pathway modeling allows us to reconstruct HMO biosynthetic pathways. Using new data mining approaches and leveraging samples and metadata from large mother-infant cohorts enable us to identify associations between HMO composition and infant and maternal health outcomes. Suitable preclinical models and clinical intervention studies allow us to corroborate the established associations for causal relationships and test for in vivo efficacy in humans. Knowledge generated from these different approaches will help us establish true structure-function relationships and provide the rigorous evidence required to improve infant health and development.
寡糖是一组复杂的聚糖，存在于大多数哺乳动物的乳汁中。然而，人乳是独特的，因为人乳寡糖 (HMOs) 的浓度远高于其他哺乳动物，其结构组成也更为复杂，并且在女性之间存在差异。这些观察结果引发了几个问题：(i) 为什么在乳寡糖方面人类是独特的？(ii) 哪些母体遗传和环境因素驱动 HMO 组成的个体间差异？(iii) 对婴儿——以及潜在的母亲——有哪些短期和长期的健康益处？全基因组关联研究、乳转录组学、体外基因编辑和计算机途径建模的结合使我们能够重建 HMO 生物合成途径。利用新的数据挖掘方法，并利用来自大型母婴队列的样本和元数据，使我们能够识别 HMO 组成与婴儿和母亲健康结果之间的关联。合适的临床前模型和临床干预研究使我们能够证实已建立的关联是否具有因果关系，并在人体中测试体内疗效。这些不同方法产生的知识将帮助我们建立真正的结构-功能关系，并提供改善婴儿健康和发育所需的严格证据。
