The association of human milk oligosaccharides with glucose metabolism in overweight and obese pregnant women

Abstract

Background Human milk oligosaccharides (HMOs) were recently found in serum of normal-weight pregnant women, with concentrations increasing from early to mid- and late pregnancy. Whether HMOs have effects on maternal metabolism is unknown. Objectives We aimed to study the presence and changes in HMOs throughout pregnancy and assess associations with maternal glucose metabolism throughout pregnancy. Methods The study was a prospective longitudinal cohort study including 87 overweight or obese women. Blood samples were taken at 15, 24, and 32 wk of pregnancy. In serum, 4 HMOs [2′-fucosyllactose (2′FL), lactodifucotetraose (LDFT), 3′-sialyllactose (3′SL), and 3′-sialyllactosamine (3′SLN)] were measured. In linear regression models, the associations between HMOs and (changes in) maternal metabolic parameters were assessed. Results All 4 HMOs showed a significant increase from 15 to 32 weeks of gestation. 3′SL and 3′SLN, but not 2′FL or LDFT, at 15 wk were positively associated with (changes in) fasting glucose at 24 and 32 wk. LDFT was positively associated with (changes in) insulin and HOMA-index at 24 but not 32 wk. A model to predict the development of gestational diabetes mellitus (GDM) that included fasting glucose, prepregnancy BMI, gestational weight gain, age, parity, smoking, and history of macrosomia resulted in an area under the curve (AUC) of 0.81 (95% CI: 0.70, 0.92). Adding 3′SL to this model increased the AUC to 0.91 (95% CI: 0.84, 0.97). Conclusions The sialylated HMOs 3′SL and 3′SLN were associated with fasting glucose; LDFT was associated with fasting insulin and HOMA-index. Furthermore, 3′SL was more predictive of future GDM diagnoses than was fasting glucose in early pregnancy. Causal relations are unclear and need further investigation.

Human Milk Oligosaccharides Modulate the Risk for Preterm Birth in a Microbiome-Dependent and -Independent Manner

“…The inflammation-associated increase in serum 3=SL seems to fit with our previous study in pregnant women at risk for GDM, which is also considered an inflammatory disorder. Serum 3=SL was higher in women who later developed GDM (16). In addition, accumulating evidence points toward increased plasma sialic acid in inflammatory pathologies such as cancer, cardiovascular diseases, and type 2 diabetes (38).…”

“…While some studies have investigated changes in HMOs in human milk as a consequence of PTB (34-36), their potential causal role in PTB has not yet been explored. Recently, we showed that serum HMOs change during preg-nancy (15,16) and that an individual HMO, 3=SL, may be predictive of gestational diabetes mellitus (GDM) (16). An early study on maternal urinary HMOs speculated about the importance of a balanced HMO profile in maintaining a healthy pregnancy (17).…”

“…Human milk oligosaccharides (HMOs) have emerged as potential novel factors involved in maintaining a healthy pregnancy. HMOs are structurally diverse, bioactive glycans in human milk that are already present in the serum (15,16) and urine of pregnant women (17,18) as early as 10 weeks of gestation. We have previously shown variations in serum HMO concentration and composition with gestational age (GA) and secretor status (15,16).…”

“…HMOs are structurally diverse, bioactive glycans in human milk that are already present in the serum (15,16) and urine of pregnant women (17,18) as early as 10 weeks of gestation. We have previously shown variations in serum HMO concentration and composition with gestational age (GA) and secretor status (15,16). Women with a positive secretor status have an active Secretor gene encoding ␣1-2 fucosyltransferase-2 (FUT2) and thus can produce ␣1-2 fucosylated HMOs.…”

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

“…In a recent study, Jantscher-Krenn et al reported an association between circulating HMO concentrations during pregnancy and maternal glucose metabolism in a cohort of overweight and obese women. Interestingly, they found that including concentrations of the HMO 3 -sialyllactose (3 SL) in a model that predicted the development of gestational diabetes mellitus significantly improved the area under the curve for the model, suggesting that HMO production during pregnancy may influence maternal glucose homeostasis [17]. Given the recent findings that HMO production begins as early as 10 weeks of pregnancy [6], it is plausible to hypothesize that maternal factors during pregnancy such as hyperglycemia, hyperinsulinemia, or insulin resistance may influence HMO synthesis all the way into lactation.…”