Neonatal diet has a large influence on child health and might modulate changes in fecal microbiota and metabolites. The aim is to investigate fecal microbiota and metabolites at different ages in infants who were breastfed (BF), received dairy-based milk formula (MF), or received soy-based formula (SF). Fecal samples were collected at 3 (n = 16, 12, and 14, respectively), 6 (n = 20, 19, and 15, respectively), 9 (n = 12, 11, and 12, respectively), and 12 mo (n = 14, 14, and 15, respectively) for BF, MF, and SF infants. Infants that breastfed until 9 mo and switched to formula were considered as no longer breastfeeding at 12 mo. Microbiota data were obtained using 16S ribosomal RNA sequencing. Untargeted metabolomics was conducted using a Q-Exactive Hybrid Quadrupole-Orbitrap mass spectrometer. The data were analyzed using R (version 3.6.0) within the RStudio (version 1.1.463) platform. At 3, 6, and 9 mo of age BF infants had the lowest α-diversity, SF infants had the highest diversity, and MF was intermediate. Bifidobacterium was 2.6- to 5-fold lower in SF relative to BF infants through 1 y of life. An unidentified genus from Ruminococcaceae higher in the SF (2%) than in the MF (0.4%) and BF (0.08%) infants at 3 mo of age was observed. In BF infants higher levels of butyric acid, d-sphingosine, kynurenic acid, indole-3-lactic acid, indole-3-acetic acid, and betaine were observed than in MF and SF infants. At 3 mo Ruminococcaceae was positively correlated to azelaic, gentisic, isocitric, sebacic, and syringic acids. At 6 mo Oscillospira was negatively correlated with 3-hydroxybutyric-acid, hydroxy-hydrocinnamic acid, and betaine whereas Bifidobacterium was negatively associated with 5-hydroxytryptamine. At 12 mo of age, Lachnospiraceae was negatively associated with hydroxyphenyllactic acid. Infant diet has a large impact on the fecal microbiome and metabolome in the first year of life.This study was registered at clinicaltrials.gov as NCT00616395.

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.

Context: It is hypothesized that obesity adversely affects the ovarian environment, which can disrupt oocyte maturation and embryonic development. Objective: This study aimed to compare oocyte gene expression profiles and follicular fluid (FF) content from overweight/obese (OW) women and normal-weight (NW) women who were undergoing fertility treatments. Design: Using single-cell transcriptomic analyses, we investigated oocyte gene expression using RNA sequencing. Patients or Other Participants: Eleven OW women and 13 NW women undergoing fertility treatments were enrolled. Main Outcome Measures: Oocyte messenger RNA profiles as well as serum and FF hormone and lipid levels were assessed. Results: OW women had significantly higher body mass index, body fat percentage, and serum homeostatic model assessment−insulin resistance index compared with NW women (P < 0.01). Serum leptin and C-reactive protein (CRP) levels as well as FF leptin, CRP, and triglyceride levels were increased (P < 0.05) in OW compared with NW women. Oocytes from OW women had increased expression of proinflammatory (CXCL2; P = 0.071) and oxidative stress–related (DUSP1; P = 0.051) genes but had decreased expression of GAS7 (fat metabolism; P = 0.065), TXNIP (oxidative stress; P = 0.055), and transcription factors ID3 (P = 0.075) and TWIST1 (P = 0.099) compared with NW women. Conclusions: These findings provide evidence for the significant influence of body composition on oocyte transcript abundance in women undergoing hormonal induction to retrieve oocytes. They further identify the potential for maternal diet to influence oocyte gene expression. The preconception period is, therefore, an important window of opportunity to consider for lifestyle interventions.

BACKGROUND AND OBJECTIVE: Although soy formula has been reported to support normal development, concerns exist regarding potential adverse developmental effects of phytochemicals associated with soy protein. This study characterized developmental status (mental, motor, and language) of breastfed (BF), milk-based formula–fed (MF), or soy protein–based formula–fed (SF) infants during the first year of life. METHODS: Healthy infants (N = 391) were assessed longitudinally at ages 3, 6, 9, and 12 months. Development was evaluated by using the Bayley Scales of Infant Development and the Preschool Language Scale-3. Mixed effects models were used while adjusting for socioeconomic status, mother’s age and IQ, gestational age, gender, birth weight, head circumference, race, age, and diet history. RESULTS: No differences were found between formula-fed infants (MF versus SF). BF infants scored slightly higher than formula-fed infants on the Mental Developmental Index (MDI) score at ages 6 and 12 months (P < .05). Infants who were breastfed also had higher Psychomotor Development Index scores than SF infants at age 6 months and slightly higher Preschool Language Scale-3 scores than MF infants at ages 3 and 6 months (P < .05). In addition, BF infants had a lower probability to score within the lower MDI quartile compared with MF infants and a higher likelihood to score within the upper quartile for the MDI and Psychomotor Development Index compared with SF infants. CONCLUSIONS: This unique study showed that all scores on developmental testing were within established normal ranges and that MF and SF groups did not differ significantly. Furthermore, this study demonstrated a slight advantage of BF infants on cognitive development compared with formula-fed infants.

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.