Third-trimester glucose homeostasis in healthy women is differentially associated with human milk oligosaccharide composition at 2 months postpartum by secretor phenotype

Authors: SABEN, JESSICA - Arkansas Children'S Nutrition Research Center (ACNC); ABRAHAM, ANN - University Of California, San Diego; BODE, LARS - University Of California, San Diego; SIMS, CLARK - Arkansas Children'S Nutrition Research Center (ACNC); ANDRES, ALINE - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/20/2020
Publication Date: 7/24/2020
Citation: Saben, J.L., Abraham, A., Bode, L., Sims, C.R., Andres, A. 2020. Third-trimester glucose homeostasis in healthy women is differentially associated with human milk oligosaccharide composition at 2 months postpartum by secretor phenotype. Nutrients. 12(8):2209. https://doi.org/10.3390/nu12082209.
DOI: https://doi.org/10.3390/nu12082209

Interpretive Summary: Human milk oligosaccharides (HMOs) are small molecules in human milk that play a critical role in infant health. Obesity and the negative effects it can have on metabolism can negatively impact lactation and change milk composition. In this study, we examined the relationship between a mother's glucose metabolism and the HMO composition of human milk in 136 healthy women with body mass indexes (BMIs) between 18.5 and 35 kg/m2. At 30 weeks of pregnancy, we measured glucose and insulin in the blood, and calculated two scores of glucose metabolism (HOMA-IR and insulin sensitivity index[ISI]) Human milk samples were collected 2 months after birth and HMOs were measured using high performance liquid chromatography. Women were categorized into "secretor" and "non-secretor" groups based 2'-Fucosyllactose concentrations. Correlation analysis and linear models were used to examine the relationships between maternal glucose metabolism and HMO concentrations. In non-secretors, 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.

Technical 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 gestation in healthy women (body mass index = 18.5 - 35 kg/m2). Human milk samples were collected at 2 months postpartum. HMO concentrations were measured via high performance liquid chromatography. Women were categorized into "secretor" and "non-secretor" groups based 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.