Third-Trimester Glucose Homeostasis in Healthy Women Is Differentially Associated with Human Milk Oligosaccharide Composition at 2 Months Postpartum by Secretor Phenotype

Abstract

Human milk oligosaccharides (HMOs) are bioactive molecules in human milk that play a critical role in infant health. Obesity and associated metabolic aberrations can negatively impact lactation and alter milk composition. Here, the relationship between maternal glucose homeostasis and HMO composition from 136 healthy women was examined. Maternal glucose homeostasis (fasting plasma glucose and insulin, homeostatic model assessment for insulin resistance, and insulin sensitivity index) was evaluated at 30 weeks of gestation in healthy women (body mass index = 18.5–35 kg/m2). Human milk samples were collected at two months postpartum. HMO concentrations were measured via high performance liquid chromatography. Women were categorized into “secretor” and “non-secretor” groups based on 2′-Fucosyllactose concentrations (<100 nmol/mL, non-secretor). Pearson’s correlation analysis and linear models were used to assess the relationships between maternal glucose homeostasis and HMO concentrations. In non-secretors, third trimester fasting plasma glucose and insulin were negatively associated with total HMO-bound sialic acid and concentrations of the sialylated HMOs 3′-sialyllactose and disialylacto-N-tetraose. In secretors, difucosyllactose and lacto-N-fucopentaose-II concentrations increased and sialyllacto-N-tetraose c and sialyllacto-N-tetraose b decreased as insulin sensitivity increased. This study is the first to demonstrate a relationship between obesity-associated maternal factors and HMO composition in both secretor and non-secretor populations.

Human Milk Oligosaccharide Concentrations and Infant Intakes Are Associated with Maternal Overweight and Obesity and Predict Infant Growth

“…Approximately 73% of the total population was phenotypically determined to be secretors, based on a human milk 2’FL concentration of >100 nmol/mL at 2 months postpartum. A greater proportion of women with OW (31.4%) or OB (33.3%) were phenotyped as non-secretors compared to women with NW (16.2%), consistent with our previous findings [ 17 ]. The overall cohort consisted mostly of Caucasian women (81.4%) who were approximately 30 years of age.…”

“…Maternal genetics (expression patterns of Secretor (Se) and Lewis (Le) gene alleles, which code for different fucosyltransferases) have the greatest impact on HMO composition [ 26 ]. However, we and several others have concluded that various maternal characteristics (age, race, ethnicity, and parity) including pre-pregnancy BMI [ 10 , 11 , 17 ] and maternal glucose homeostasis [ 17 ] can affect HMO composition during lactation. To our knowledge, this study presented herein is one of the first to explore the relationship between maternal BMI and HMO composition in a large group of women whose BMIs encompassed Class I–Class III obesity.…”

“…Although the mechanisms driving the observed differences in HMO composition with increasing maternal BMI have not been elucidated, it is likely both physiological and environmental factors that contribute to altered HMO synthesis [ 10 ]. We have previously demonstrated that glucose homeostasis during pregnancy is associated with HMO composition at 2 months postpartum [ 17 ]. In particular, maternal insulin levels and measures of insulin sensitivity were associated with total HMO and sialylated HMO concentrations in non-secretors.…”

“…Enrollment criteria have been previously described in detail elsewhere for NCT01131117 [ 16 ]. Please see [ 5 , 17 , 18 ] for previously published data on human milk analyses from these cohorts. Women were recruited prior to pregnancy or during the first trimester of pregnancy.…”

Human Milk Oligosaccharides: Their Effects on the Host and Their Potential as Therapeutic Agents

“…This lack of HMOs may induce consequences for metabolic activities, especially diarrheal diseases, in infants (23). On the other hand, women without functional FUT3 cannot produce HMOs with a1,3/4 fucosyl linkages such as 3'-FL and LNFPII (24). Recently, glucose levels in the blood of the mother were shown to affect the composition of HMOs in breastmilk.…”