Chloe Yonemitsu

Growing evidence indicates that human milk oligosaccharides (HMOs) are important bioactive compounds that enhance health and developmental outcomes in breastfed babies. Maternal dietary intake likely contributes to variation in HMO composition, but studies identifying diet–HMO relationships are few and inconsistent. This study aimed to investigate how the maternal intake of macronutrients and micronutrients—specifically proteins, fats, vitamins, and minerals—associated with HMOs at 1 month (n = 210), 6 months (n = 131), and 12 months postpartum (n = 84). Several associations between maternal dietary factors and HMO profiles were identified utilizing partial correlation analysis. For example, maternal free sugar (rho = −0.02, p < 0.01), added sugar (rho = −0.22, p < 0.01), and sugary sweetened beverage (rho = −0.22, p < 0.01) intake were negatively correlated with the most abundant HMO, 2′-fucosyllactose (2′-FL), at 1 month, suggesting that higher sugar consumption was associated with reduced levels of 2′-FL. Further, vitamins D, C, K, and the minerals zinc and potassium were positively correlated with 2′-FL at 1 month (p_All < 0.05). For the longitudinal analysis, a mixed-effects linear regression model revealed significant associations between maternal vitamin intake and HMO profiles over time. For example, for each unit increase in niacin intake, there was a 31.355 nmol/mL increase in 2′-FL concentration (p = 0.03). Overall, the results provide additional evidence supporting a role for maternal nutrition in shaping HMO profiles, which may inform future intervention strategies with the potential of improving infant growth and development through optimal HMO levels in mothers’ milk.

Background & Objective: Human milk oligosaccharides ( HMOs) have been associated with several child growth metrics, but there was no difference in the associations according to child sex. Here, we present clinic-based cross-sectional data on the relationship between specific HMOs in the milk of Ugandan mothers and growth in their breastfed children as a group and as males and females separately. Method: Human milk samples were manually collected from 127 lactating mothers. Levels of human milk oligosaccharides (HMOs) were analyzed by high-performance liquid chromatography (HPLC). Children’s weight and length were measured using a portable digital scale and length board, respectively. Weight-for-age (WAZ), height-for-age (HAZ) and weight for height (WHZ) Z scores were calculated. The relationships between HMOs and untransformed weights and heights and between WAZ, HAZ and WHZ subcategories were analyzed for all children and for males and females separately by Spearman’s correlation and Kruskal‒Wallis and Mann‒Whitney U tests. Results: There were positive and negative correlations between the concentrations of specific HMOs and the heights and weights of children according to mothers’ secretor status. Tall infant stature was associated with higher concentrations of 6’SL, LSTc, DFLNH, DSLNH, LNnT and total HMOs in secretor or nonsecretor mothers; short infant stature was associated with higher concentrations of 3FL and DFLac; overweight was associated with higher concentrations of 6’SL, LSTc and LNnT in secretor and nonsecretor mothers; and normal weight was associated with higher concentrations of 3’FL. The associations between maternal HMO levels and childrens heights and weights or between the LAZ, WAZ and WHZ subcategories significantly differed between male and female children. Conclusions: There are sex differences in the associations between high concentrations of some HMOs and stature and weight in Ugandan children born to secretor and nonsecretor mothers. Highlights: This study showed that some HMOs are associated with child growth metrics in a sex-specific pattern. Four HMOs (3FL, DSLNT, DFLac, and 3’SL) were positively correlated with the height/length of the children. There were significant positive correlations between height/length and 3FL and DSLNT in only female children and between height/length and DFLac in only male children. DSLNT, DFLac and LSTb were positively correlated with weight in female and male children respectively. Plain Language Summary: Human milk oligosaccharides ( HMOs) have been associated with growth parameters of children in the Americas, Europe and Asia. Only two such studies have been conducted in Africa. None of the studies investigated the relationship between child sex and HMO composition and growth interactions. We examined the relationship between 19 well-characterized HMOs and growth metrics and also dissected the data by infant sex. Our results show a positive correlation between some HMOs and growth indices in either female or male children only. This highlights the impact of sex differences in the relationship between specific HMOs and growth measures in children. This evidence, if validated, could inform future nutritional interventions involving combinations of HMOs as food supplements that are equally effective for both male and female children.

Background: Human milk oligosaccharides (HMOs) protect against infection and promote growth and cognitive development in breastfeeding children. Non-genetic factors which influence HMO composition in breastfeeding mothers in rural Africa have not been investigated. Objective: We undertook a cross-sectional study to determine the association between HMO profiles and non-genetic maternal factors and children’s sex in Ugandan mother-children pairs. Method: Human milk was collected from 127 breastfeeding mothers by manual expression. HMO analysis was by high performance liquid chromatography. The proportion of each HMO per total HMO concentration was calculated. Spearman’s correlation and Mann-Whitney U test were used to assess the relationship between individual HMOs and maternal factors and infant sex. Result: Nineteen HMOs were assayed. The prevalence of secretor and non-secretor status, based on the proportion of mothers with high milk concentrations of 2’FL and LNFP 1, was 80.3 % and 19.7 %, respectively. In secretor mothers, 2’FL, DFLac and LNFP I constituted > 57 % while in non-secretor mothers LNT and LNFPII constituted 46.9 % of the measured total HMOs. The median 3’SL concentration in milk of all mothers of male children was significantly higher than that in all mothers of female children. The median DFLac concentration in all mothers was significantly higher in multiparous mothers compared to primiparous mothers. Higher FDSLNH and lower LNH concentrations were observed in overweight secretor and non-secretor mothers, respectively. Median concentrations of LNFP I and DSLNT were significantly higher in all mothers < 18 years old compared all mothers > 18 years old. Concentrations of specific HMOs increased, decreased, or remained unchanged with increasing lactation duration in secretor and non-secretor mothers. Conclusions: Specific HMOs were associated with infant sex and maternal age, parity and post-partum BMI in Ugandan mothers but were different from those reported in other populations.

Animal studies have shown that human milk oligosaccharides (HMOs) are important in early brain development, yet their roles have not been assessed in humans. The purpose of this study was to determine the associations of HMOs with MRI indices of tissue microstructure and regional cerebral blood flow (rCBF) in infants. Mother–infant pairs (N = 20) were recruited at 1 month postpartum. Milk was assayed for the concentrations of the HMOs 2′-fucosyllactose (2′FL), 3-fucosyllactose (3FL), 3′-sialyllactose (3′SL), and 6′-sialyllactose (6′SL). Diffusion and arterial spin labeling measures were acquired using a 3.0-Tesla MRI scanner. Multiple linear regression was used to assess the voxel-wise associations of HMOs with fractional anisotropy (FA), mean diffusivity (MD), and rCBF values across the brain. After adjusting for pre-pregnancy BMI, sex, birthweight, and postmenstrual age at time of scan, a higher 2′FL concentration was associated with reduced FA, increased MD, and reduced rCBF in similar locations within the cortical mantle. Higher 3FL and 3′SL concentrations were associated with increased FA, reduced MD, and increased rCBF in similar regions within the developing white matter. The concentration of 6′SL was not associated with MRI indices. Our data reveal that fucosylated and sialylated HMOs differentially associate with indices of tissue microstructure and rCBF, suggesting specific roles for 2′FL, 3FL, and 3′SL in early brain maturation.

Human milk oligosaccharide (HMO) composition varies throughout lactation and can be influenced by maternal characteristics. This study describes HMO variation up to three months postpartum and explores the influences of maternal sociodemographic and anthropometric characteristics in a Brazilian prospective cohort. We followed 101 subjects from 28–35 gestational weeks (baseline) and throughout lactation at 2–8 (visit 1), 28–50 (visit 2) and 88–119 days postpartum (visit 3). Milk samples were collected at visits 1, 2 and 3, and 19 HMOs were quantified usinghigh-performance liquid chromatography with fluorescence detection (HPLC-FL). Friedman post-hoc test, Spearman rank correlation for maternal characteristics and HMOs and non-negative matrix factorization (NMF) were used to define the HMO profile. Most women were secretors (89.1%) and presented high proportion of 2′-fucosyllactose (2′FL) at all three sample times, while lacto-N-tetraose (LNT, 2–8 days) and lacto-N-fucopentaose II (LNFPII, 28–50 and 88–119 days) were the most abundant HMOs in non-secretor women. Over the course of lactation, total HMO weight concentrations (g/L) decreased, but total HMO molar concentrations (mmol/L) increased, highlighting differential changes in HMO composition over time. In addition, maternal pre-pregnancy body mass index (BMI) and parity influence the HMO composition in healthy women in this Brazilian cohort.