Maternal obesity increases placental transport of macronutrients, resulting in fetal overgrowth and obesity later in life. Choline participates in fatty acid metabolism, serves as a methyl donor, and influences growth signaling, which may modify placental macronutrient homeostasis and affect fetal growth. Using a mouse model of maternal obesity, we assessed the effect of maternal choline supplementation on preventing fetal overgrowth and restoring placental macronutrient homeostasis. C57BL/6J mice were fed either a high-fat (HF, 60% kcal from fat) diet or a normal (NF, 10% kcal from fat) diet with a drinking supply of either 25 mM choline chloride or control purified water, respectively, beginning 4 weeks prior to mating until gestational day 12.5. Fetal and placental weight, metabolites, and gene expression were measured. HF feeding significantly (P < 0.05) increased placental and fetal weight in the HF-control (HFCO) versus NF-control (NFCO) animals, whereas the HF choline-supplemented (HFCS) group effectively normalized placental and fetal weight to the levels of the NFCO group. Compared to HFCO, the HFCS group had lower (P < 0.05) glucose transporter 1 (GLUT1) and fatty acid transport protein 1 (FATP1) expression as well as lower accumulation of glycogen in the placenta. The HFCS group also had lower (P < 0.05) placental 4E-binding protein 1 and ribosomal protein s6 phosphorylation, which are indicators of mechanistic target of rapamycin complex 1 (mTORC1) activation favoring macronutrient anabolism. In summary, our results suggest that maternal choline supplementation prevented fetal overgrowth in obese mice at mid-gestation and improved biomarkers of placental macronutrient homeostasis.

Background Human milk contains a diverse community of bacteria that are modified by maternal factors, but whether these or other factors are similar in developing countries has not been explored. Our objective was to determine whether milk microbiota was modified by maternal age, body mass index (BMI), parity, lactation stage, subclinical mastitis (SCM), and breastfeeding practices in the first six months of lactation in an indigenous population from Guatemala. Methods For this cross-sectional study, Mam-Mayan indigenous mothers nursing infants &lt;6 months of age were recruited. Unilateral human milk samples were collected (n = 86) and processed for 16S rRNA sequencing at the genus level. Microbial diversity and relative abundance were compared with maternal factors (age, BMI, parity, stage of lactation, SCM and 3 breastfeeding practices (exclusive, predominant, mixed)) obtained through questionnaires. Results Streptococcus was the most abundant genus (33.8%), followed by Pseudomonas (18.7%) and Sphingobium (10.7%) but relative abundance was associated with maternal factors. First, Lactobacillus and Streptococcus were more abundant in early lactation whereas the common oral (Leptotrichia) and environmental (Comamonas) bacteria were more abundant in established lactation. Second, Streptococcus, Lactobacillus, Lactococcus, Leuconostoc and Micrococcus had higher abundance in multiparous mothers compared to primiparous mothers. Third, a more diverse microbiota characterized by higher abundance of lactic acid bacteria (Lactobacillus, Leuconostoc and Lactococcus), Leucobacter and Micrococcus was found in mothers with a healthy BMI. Finally, distinct microbial communities differed by stage of lactation and by exclusive, predominant or mixed breastfeeding practices. Conclusion Milk bacterial communities in an indigenous community were associated with maternal factors. Higher microbial diversity was supported by having a healthy BMI, the absence of SCM and by breastfeeding. Interestingly, breastfeeding practices when assessed by lactation stage were associated with distinct microbiota profiles.

Human milk contains abundant commensal bacteria that colonize and establish the infant’s gut microbiome but the association between the milk microbiome and head circumference during infancy has not been explored. For this cross-sectional study, head-circumference-for-age-z-scores (HCAZ) of vaginally delivered breastfed infants were collected from 62 unrelated Mam-Mayan mothers living in eight remote rural communities in the Western Highlands of Guatemala during two stages of lactation, ‘early’ (6–46 days postpartum, n = 29) or ‘late’ (109–184 days postpartum, n = 33). At each stage of lactation, infants were divided into HCAZ ≥ −1 SD (early: n = 18; late: n = 14) and HCAZ &lt; −1 SD (early: n = 11; late: n = 19). Milk microbiome communities were assessed using 16S ribosomal RNA gene sequencing and DESeq2 was used to compare the differential abundance (DA) of human milk microbiota with infant HCAZ subgroups at both stages of lactations. A total of 503 ESVs annotated 256 putative species across the 64 human milk samples. Alpha-diversity using Chao index uncovered a difference in microbial community richness between HCAZ ≥ −1 SD and HCAZ &lt; −1 SD groups at late lactation (p = 0.045) but not at early lactation. In contrast, Canonical Analysis of Principal Coordinates identified significant differences between HCAZ ≥ −1 SD and HCAZ &lt; −1 SD at both stages of lactation (p = 0.003); moreover, 26 milk microbial taxa differed in relative abundance (FDR &lt; 0.05) between HCAZ ≥ −1 SD and HCAZ &lt; −1 SD, with 13 differentially abundant at each lactation stage. Most species in the HCAZ ≥ −1 SD group were Streptococcus species from the Firmicutes phylum which are considered human colonizers associated with human milk whereas the HCAZ &lt; −1 SD group at late lactation had more differentially abundant taxa associated with environmentally and ‘potentially opportunistic’ species belonging to the Actinobacteria genus. These findings suggest possible associations between brain growth of breastfed infants and the milk microbiome during lactation. Importantly, these data provide the first evidence of cross talk between the human milk microbiome and the infant brain that requires further investigation.