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Human Milk Exosomal MicroRNA: Associations with Maternal Overweight/Obesity and Infant Body Composition at 1 Month of Life.

ABSTRACT: Among all the body fluids, breast milk is one of the richest sources of microRNAs (miRNAs). MiRNAs packaged within the milk exosomes are bioavailable to breastfeeding infants. The role of miRNAs in determining infant growth and the impact of maternal overweight/obesity on human milk (HM) miRNAs is poorly understood. The objectives of this study were to examine the impact of maternal overweight/obesity on select miRNAs (miR-148a, miR-30b, miR-29a, miR-29b, miR-let-7a and miR-32) involved in adipogenesis and glucose metabolism and to examine the relationship of these miRNAs with measures of infant body composition in the first 6 months of life. Milk samples were collected from a cohort of 60 mothers (30 normal-weight [NW] and 30 overweight [OW]/obese [OB]) at 1-month and a subset of 48 of these at 3 months of lactation. Relative abundance of miRNA was determined using real-time PCR. The associations between the miRNAs of interest and infant weight and body composition at one, three, and six months were examined after adjusting for infant gestational age, birth weight, and sex. The abundance of miR-148a and miR-30b was lower by 30% and 42%, respectively, in the OW/OB group than in the NW group at 1 month. miR-148a was negatively associated with infant weight, fat mass, and fat free mass, while miR-30b was positively associated with infant weight, percent body fat, and fat mass at 1 month. Maternal obesity is negatively associated with the content of select miRNAs in human milk. An association of specific miRNAs with infant body composition was observed during the first month of life, suggesting a potential role in the infant's adaptation to enteral nutrition.

SUBMITTER: Shah KB

PROVIDER: S-EPMC8066780 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMaternal obesity is a risk factor for childhood obesity; this is a major public health concern given that ∼40% of pregnant women are either overweight or obese. Whether differences in milk composition in lean compared with obese women contribute to childhood obesity is unclear.ObjectivesWe aimed to analyze relationships between maternal obesity and human milk metabolites, infant body composition, and postnatal weight gain.MethodsThis was a prospective study in which mothers intending to breastfeed exclusively, and their newborn infants, were enrolled at delivery (n = 35 mother-infant pairs). We excluded mothers with diabetes, other medical conditions, or pregnancy complications. Participants were grouped by maternal prepregnancy BMI <25 (lean) or ≥25 kg/m2 (overweight/obese). We analyzed infant body composition by dual-energy X-ray absorptiometry and used untargeted liquid chromatography-gas chromatography-mass spectrometry to measure the milk content of 275 metabolites at 1 and 6 mo postpartum.ResultsAt 1 mo postpartum, 10 metabolites differed between overweight/obese and lean groups with nominal P < 0.05, but none was altered with a false discovery rate <0.25. Many differentially abundant metabolites belonged to the same chemical class; e.g., 4/10 metabolites were nucleotide derivatives, and 3/10 were human milk oligosaccharides. Milk adenine correlated positively with both continuously distributed maternal BMI and with infant adiposity and fat accrual. Analysis of milk composition at 6 mo postpartum revealed 20 differentially abundant metabolites (P < 0.05) in overweight/obese compared with lean women, including 6 metabolites with a false discovery rate of <0.25. At both 1 and 6 mo, human milk abundance of 1,5-anhydroglucitol, which has not previously been described in milk, was positively associated with maternal BMI.ConclusionsMaternal obesity is associated with changes in the human milk metabolome. While only a subset of metabolites correlated with both maternal and infant weight, these point to potential milk-dependent mechanisms for mother-child transmission of obesity. This trial was registered at www.clinicaltrials.gov as NCT02535637.

Project description:IntroductionIngestion of human milk (HM) is identified as a significant factor associated with early infant gut microbial colonization, which has been associated with infant health and development. Maternal diet has been associated with the HM microbiome (HMM). However, a few studies have explored the associations among maternal diet, HMM, and infant growth during the first 6 months of lactation.MethodsFor this cross-sectional study, Mam-Mayan mother-infant dyads (n = 64) were recruited from 8 rural communities in the Western Highlands of Guatemala at two stages of lactation: early (6-46 days postpartum, n = 29) or late (109-184 days postpartum, n = 35). Recruited mothers had vaginally delivered singleton births, had no subclinical mastitis or antibiotic treatments, and breastfed their infants. Data collected at both stages of lactation included two 24-h recalls, milk samples, and infant growth status indicators: head-circumference-for-age-z-score (HCAZ), length-for-age-z-score (LAZ), and weight-for-age-z-score (WAZ). Infants were divided into subgroups: normal weight (WAZ ≥ -1SD) and mildly underweight (WAZ < -1SD), non-stunted (LAZ ≥ -1.5SD) and mildly stunted (LAZ < -1.5SD), and normal head-circumference (HCAZ ≥ -1SD) and smaller head-circumference (HCAZ < -1SD). HMM was identified using 16S rRNA gene sequencing; amplicon analysis was performed with the high-resolution ANCHOR pipeline, and DESeq2 identified the differentially abundant (DA) HMM at the species-level between infant growth groups (FDR < 0.05) in both early and late lactation.ResultsUsing both cluster and univariate analyses, we identified (a) positive correlations between infant growth clusters and maternal dietary clusters, (b) both positive and negative associations among maternal macronutrient and micronutrient intakes with the HMM at the species level and (c) distinct correlations between HMM DA taxa with maternal nutrient intakes and infant z-scores that differed between breast-fed infants experiencing growth faltering and normal growth in early and late lactation.ConclusionCollectively, these findings provide important evidence of the potential influence of maternal diet on the early-life growth of breastfed infants via modulation of the HMM.

Project description:Background - Prepregnancy overweight and obesity promote deleterious health impacts on both mothers during pregnancy and the offspring. Significant changes in the maternal peripheral blood mononuclear cells (PBMCs) gene expression due to obesity are well-known. However, during pregnancy the impact of overweight on immune cell gene expression and its association with maternal and infant outcomes is not well explored. Methods – Blood samples were collected from healthy normal weight (NW, BMI 18.5-24.9) or overweight (OW, BMI 25-29.9) 2nd parity pregnant women at 12, 24 and 36 weeks of pregnancy. PBMCs were isolated from the blood and subjected to mRNA sequencing. Maternal and infant microbiota were analyzed by 16S rRNA gene sequencing. Integrative multi-omics data analysis was performed to evaluate the association of gene expression with maternal diet, gut microbiota, milk composition, and infant gut microbiota. Results - Gene expression analysis revealed that 453 genes were differentially expressed in the OW women compared to NW women at 12 weeks of pregnancy, out of which 354 were upregulated and 99 were downregulated. Several up-regulated genes in the OW group were enriched in inflammatory, chemokine-mediated signaling and regulation of interleukin-8 production-related pathways. At 36 weeks of pregnancy healthy eating index score was positively associated with several genes that include, DTD1, ELOC, GALNT8, ITGA6-AS1, KRT17P2, NPW, POT1-AS1 and RPL26. In addition, at 36 weeks of pregnancy, genes involved in adipocyte functions, such as NG2 and SMTNL1, were negatively correlated to human milk 2’FL and total fucosylated oligosaccharides content collected at 1 month postnatally. Furthermore, infant Akkermansia was positively associated with maternal PBMC anti-inflammatory genes that include CPS1 and RAB7B, at 12 and 36 weeks of pregnancy. Conclusions – These findings suggest that prepregnancy overweight impacts the immune cell gene expression profile, particularly at 12 weeks of pregnancy. Further, deciphering the complex association of PBMC’s gene expression levels with maternal gut microbiome and milk composition and infant gut microbiome may aid in developing strategies to mitigate obesity-mediated effects.

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Human Milk Exosomal MicroRNA: Associations with Maternal Overweight/Obesity and Infant Body Composition at 1 Month of Life.

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