Developmental Origins of Chronic Diseases in Children Network (DEVOTION), Children's Hospital Research Institute of Manitoba, Department of Pediatrics and Child Health.
Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Canada.
J Nutr. 2018 Nov 1;148(11):1733-1742. doi: 10.1093/jn/nxy175.
Human milk oligosaccharides (HMOs) shape the developing gut microbiome and influence immune function. Aside from genetic Secretor status, the factors influencing HMO synthesis and secretion are largely unknown.
We aimed to identify modifiable and nonmodifiable factors associated with HMO concentrations.
This prospective observational study included a representative subset of 427 mothers participating in the CHILD birth cohort (mean age: 33 y, 73% Caucasian). Breast milk was collected at 3-4 mo postpartum. Concentrations of 19 predominant HMOs were measured by rapid high-throughput HPLC. Secretor status was defined by the presence of 2'-fucosylactose. Associations with maternal, infant, and environmental factors were explored using multivariable regression. Breastfeeding duration was explored as a secondary outcome.
Overall, 72% of mothers were Secretors and the mean ± SD duration of any breastfeeding was 12.8 ± 5.7 mo. HMO profiles were highly variable; total HMO concentrations varied 3.7-fold and individual HMOs varied 20- to >100-fold. Secretor mothers had higher total HMO concentrations than did non-Secretors (mean: 15.91 ± 2.80 compared with 8.94 ± 1.51 μmol/mL, P < 0.001) and all individual HMOs differed by Secretor status, except for disialyllacto-N-tetraose (DSLNT). Most HMO concentrations were lower in milk collected later in lactation, although some were higher including DSLNT and 3'-sialyllactose. Independent of Secretor status and lactation stage, seasonal and geographic variation was observed for several HMOs. Parity, ethnicity, and breastfeeding exclusivity also emerged as independent factors associated with some HMOs, whereas diet quality and mode of delivery did not. Together, these factors explained between 14% (for 6'-sialyllactose) and 92% (for 2'-fucosyllactose) of the observed variation in HMO concentrations. Lower concentrations of lacto-N-hexaose or fucodisialyllacto-N-hexaose were associated with earlier breastfeeding cessation.
HMO concentrations vary widely between mothers and are associated with multiple characteristics beyond genetic Secretor status, as well as feeding practices and environmental factors. Further research is warranted to determine how these associations affect infant health. This study was registered at clinicaltrials.gov as NCT03225534.
人乳寡糖（HMOs）塑造了肠道微生物群的发育，并影响了免疫功能。除了遗传 Secretor 状态外，影响 HMO 合成和分泌的因素在很大程度上尚不清楚。
我们旨在确定与 HMO 浓度相关的可改变和不可改变的因素。
本前瞻性观察性研究纳入了参与 CHILD 出生队列的 427 位代表性母亲中的一部分（平均年龄：33 岁，73%为白种人）。在产后 3-4 个月收集母乳。通过快速高通量 HPLC 测定 19 种主要 HMO 的浓度。通过存在 2'-岩藻糖基乳糖来定义 Secretor 状态。使用多变量回归探讨了与母亲、婴儿和环境因素的相关性。母乳喂养持续时间作为次要结局进行了探讨。
总体而言，72%的母亲为 Secretors，母乳喂养的平均持续时间为 12.8±5.7 个月。HMO 谱高度可变；总 HMO 浓度差异 3.7 倍，个别 HMO 差异 20-100 倍。Secretor 母亲的总 HMO 浓度高于非 Secretor 母亲（平均值：15.91±2.80 与 8.94±1.51 μmol/mL，P<0.001），并且所有个体 HMO 都因 Secretor 状态而异，除了二唾液酸乳糖-N-四糖（DSLNT）外。大多数 HMO 浓度在泌乳后期较低，尽管有些浓度较高，包括 DSLNT 和 3'-唾液酸乳糖。独立于 Secretor 状态和泌乳阶段，观察到几个 HMO 存在季节性和地理差异。产次、种族和母乳喂养的排他性也成为与某些 HMO 相关的独立因素，而饮食质量和分娩方式则不是。这些因素共同解释了 HMO 浓度观察到的变异的 14%（6'-唾液酸乳糖）至 92%（2'-岩藻糖基乳糖）。乳-N-己糖酸或岩藻糖二唾液酸-N-己糖酸的浓度较低与母乳喂养较早停止有关。
HMO 浓度在母亲之间差异很大，并且与遗传 Secretor 状态以及喂养方式和环境因素以外的多种特征相关。需要进一步研究以确定这些关联如何影响婴儿的健康。本研究在 clinicaltrials.gov 上注册为 NCT03225534。
