Abstract

Human milk oligosaccharides (HMOs) are indigestible carbohydrates with prebiotic, pathogen decoy, and immunomodulatory activities that are theorized to substantially impact infant health. The objective of this study was to monitor HMO concentrations over one year to develop a long-term longitudinal dataset. HMO concentrations in the breast milk of healthy lactating mothers of the Cambridge Baby Growth and Breastfeeding Study (CBGS-BF) were measured at birth, 2 weeks, 6 weeks, 3 months, 6 months and 12 months postpartum. HMO quantification was conducted by high-performance anion-exchange chromatography with pulsed amperometric detection using a newly validated “dilute-and-shoot” method. This technique minimizes sample losses and expedites throughput, making it particularly suitable for the analysis of large sample sets. Varying patterns of individual HMO concentrations were observed with changes in lactation timepoint and maternal secretor status, with the most prominent temporal changes occurring during the first 3 months. This data provides valuable information for the development of human milk banks in view of targeted distribution of donor milk based on infant age. Maternal FUT2 genotype was determined based on identification at single-nucleotide polymorphism rs516246 and compared with the genotype expected based on phenotypic markers in the HMO profile. Surprisingly, two mothers genotyped as secretors produced milk that displayed very low levels of 2′-fucosylated moieties. This unexpected discrepancy between genotype and phenotype suggests that differential enzyme expression may cause substantial variation in HMO profiles between genotypically similar mothers, and current genotypic methods of secretor status determination may require validation with HMO markers from milk analysis.

中文翻译：

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一项为期一年的英国健康母亲母乳中人乳寡糖谱及其与母体 FUT2 基因型关系的研究

摘要

人乳寡糖 (HMO) 是一种难以消化的碳水化合物，具有益生元、病原体诱饵和免疫调节活性，理论上可以显着影响婴儿健康。本研究的目的是监测一年内的 HMO 浓度，以开发长期纵向数据集。剑桥婴儿生长和母乳喂养研究 (CBGS-BF) 的健康哺乳母亲母乳中的 HMO 浓度在出生、2 周、6 周、3 个月、6 个月和 12 个月后测量。HMO 定量是通过高性能阴离子交换色谱和脉冲安培检测，使用新验证的“稀释和喷射”方法进行的。该技术最大限度地减少了样品损失并加快了通量，使其特别适用于大型样品集的分析。随着泌乳时间点和母体分泌状态的变化，观察到个体 HMO 浓度的不同模式，最显着的时间变化发生在前 3 个月。鉴于根据婴儿年龄有针对性地分配供体母乳，这些数据为母乳库的发展提供了有价值的信息。基于单核苷酸多态性 rs516246 的鉴定确定母体 FUT2 基因型，并与基于 HMO 谱中的表型标记预期的基因型进行比较。令人惊讶的是，两名被基因分型为分泌者的母亲生产的乳汁中 2'-岩藻糖基化部分的水平非常低。