Human milk oligosaccharides (HMOs) are bioactive molecules playing a critical role in infant health. We aimed to quantify the composition of HMOs of women with normal weight (18.5–24.9 kg/m²), overweight (25.0–29.9 kg/m²), or obesity (30.0–60.0 kg/m²) and determine the effect of HMO intake on infant growth. Human milk (HM) samples collected at 2 months (2 M; n = 194) postpartum were analyzed for HMO concentrations via high-performance liquid chromatography. Infant HM intake, anthropometrics and body composition were assessed at 2 M and 6 M postpartum. Linear regressions and linear mixed-effects models were conducted examining the relationships between maternal BMI and HMO composition and HMO intake and infant growth over the first 6 M, respectively. Maternal obesity was associated with lower concentrations of several fucosylated and sialylated HMOs and infants born to women with obesity had lower intakes of these HMOs. Maternal BMI was positively associated with lacto-N-neotetraose, 3-fucosyllactose, 3-sialyllactose and 6-sialyllactose and negatively associated with disialyllacto-N-tetraose, disialyllacto-N-hexaose, fucodisialyllacto-N-hexaose and total acidic HMOs concentrations at 2 M. Infant intakes of 3-fucosyllactose, 3-sialyllactose, 6-sialyllactose, disialyllacto-N-tetraose, disialyllacto-N-hexaose, and total acidic HMOs were positively associated with infant growth over the first 6 M of life. Maternal obesity is associated with changes in HMO concentrations that are associated with infant adiposity.

Studies indicate that maternal weight status modulates human milk composition; however, results are conflicting. Our objective was to examine the relation between maternal body composition and human milk macronutrients and bioactive components and also their association with infant daily intakes and body composition. Human milk samples were obtained from a longitudinal study (NCT 01131117) in normal weight (NW: 18.5–24.9 kg/m², n = 88) and overweight/obese (OW: 25–35 kg/m², n = 86) women between 0.5 and 9 mo postpartum. Macronutrient content was estimated using mid-infrared spectroscopy. Leptin, insulin, and C-reactive protein (CRP) were measured using electrochemiluminescence immunoassays. Infant body composition was obtained using quantitative MRI. Linear mixed models were adjusted for postpartum age and infant sex. Human milk in OW mothers was higher in fat and protein and lower in carbohydrate content at some time points compared with that in NW mothers. Human milk leptin, insulin, and CRP concentrations were higher in OW mothers compared with NW mothers, with infants of OW mothers exposed to 1.5–2.5 times higher concentrations of leptin and insulin compared with infants of NW mothers. Similar results were observed when concentrations were normalized to infant daily intake and body weight. The effect sizes of infant daily intakes associated with infant growth parameters were small for macronutrients [0.005–0.05 z-score units and 0.02–0.45 fat mass index (FMI) or fat-free mass index units per unit of change in composition, P < 0.05]. Larger effect sizes were seen with human milk insulin and leptin (0.24 z-score units and 0.37–1.15 FMI units per unit of change in composition, P < 0.05). These findings demonstrate that infants of OW mothers are exposed to higher concentrations of insulin, leptin, and, to a lesser extent, CRP. The bioavailability of these 3 human milk bioactives and their mechanisms of action in the infant are unclear. This trial was registered at clinicaltrials.gov as NCT01131117.

Maternal body composition, gestational weight gain (GWG) and diet quality influence offspring obesity risk. While the gut microbiome is thought to play a crucial role, it is understudied in pregnancy. Using a longitudinal pregnancy cohort, maternal anthropometrics, body composition, fecal microbiome and dietary intake were assessed at 12, 24 and 36 weeks of gestation. Fecal samples (n = 101, 98 and 107, at each trimester, respectively) were utilized for microbiome analysis via 16S rRNA amplicon sequencing. Data analysis included alpha- and beta-diversity measures and assessment of compositional changes using MaAsLin2. Correlation analyses of serum metabolic and anthropometric markers were performed against bacterial abundance and predicted functional pathways. α-diversity was unaltered by pregnancy stage or maternal obesity status. Actinobacteria, Lachnospiraceae, Akkermansia, Bifidobacterium, Streptococcus and Anaerotuncus abundances were associated with gestation stage. Maternal obesity status was associated with increased abundance of Lachnospiraceae, Bilophila, Dialister and Roseburia. Maternal BMI, fat mass, triglyceride and insulin levels were positively associated with Bilophila. Correlations of bacterial abundance with diet intake showed that Ruminococcus and Paraprevotella were associated with total fat and unsaturated fatty acid intake, while Collinsella and Anaerostipes were associated with protein intake. While causal relationships remain unclear, collectively, these findings indicate pregnancy- and maternal obesity-dependent interactions between dietary factors and the maternal gut microbiome.

Human milk composition is altered by maternal obesity. The association between milk metabolites and infant outcomes has not been thoroughly investigated. This study aimed to quantify maternal adiposity-related differences in the human milk metabolome and to identify metabolites associated with infant adiposity during the first 6 mo postpartum using untargeted metabolomics. Maternal anthropometrics were assessed ≤14 weeks of gestation. Human milk samples were collected at 0.5 mo (n = 159), 2 mo (n = 131), and 6 mo (n = 94) postpartum from normal weight (NW, BMI = 18.5–24.9 kg/m²) and obese (OB, BMI >30 kg/m²) mothers. GC-time-of-flight-MS was used to identify metabolic signatures that discriminate NW and OB women. Partial least squared (PLS)-discriminant analysis, and PLS-regression models were assessed to examine relations between metabolites and maternal BMI and fat mass. Metabolites altered by maternal obesity were used in linear mixed effect models to predict infant adiposity. Multivariate modeling identified 23, 17, and 10 metabolites that described maternal adiposity indices at 0.5 mo, 2 mo, and 6 mo postpartum, respectively. Monosaccharides and sugar alcohols were the most representative annotated metabolite classes that were increased in milk from OB women and included: mannose, ribose, lyxose, lyxitol (0.5 mo); mannose, ribitol, glycerol, isothreonic acid, lyxitol (2 mo); lyxitol and isothreonic acid (6 mo). Other discriminant metabolites included: 1-monostearin, xylonolactone, shikimic acid, pseudo uridine, and dodecanol (0.5 mo); N-acetyl-D-hexosamine and fumaric acid (2 mo); uric acid and tyrosine (6 mo). Mannose, lyxitol, and shikimic acid predicted higher infant adiposity over the first 6 mo of life. This study reports on 1 of the largest cohorts to date examining the metabolic profiles in human milk comparing NW and OB women. Maternal adiposity was associated with increased amounts of milk nonglucose monosaccharides. Human milk metabolomics may be useful in predicting infant adiposity. These trials were registered at www.clinicaltrials.gov as NCT01131117 and NCT02125149.