Project description:An untargeted metabolomics analysis of human milk was performed to test the hypothesis that a unique human milk metabolome would emerge based on maternal adiposity (maternal fat mass and body mass index). This study also aimed to identify differentially expressed milk metabolites that are associated with fat mass in the infant. To our knowledge this study reports on the largest cohort to date examining the metabolomic differences in human milk composition between normal weight and obese women. Data generated from this study indicate the need for further research in the area of human milk metabolomics and the potential role for human milk small molecules in contributing to offspring growth and development.
Project description:Maternal health and diet can have important consequences for offspring nutrition and metabolic health. Signals are communicated from the mother to the infant during lactation through milk via macronutrients, hormones and bioactive molecules. In this study we designed experiments to probe the mother-milk-infant triad in the condition of normal maternal health and upon exposure to high fat diet (HFD) with or without concurrent metformin exposure. We examined maternal characteristics, milk composition and offspring metabolic parameters on postnatal day 16, prior to offspring beginning to wean. We found that lactational HFD increased maternal adipose tissue, mammary gland adipocytes, and altered milk lipid composition causing a higher amount of n-6 long chain fatty acids and lower n-3. Offspring of HFD dams were heavier with more body fat during suckling. Metformin exposure decreased maternal glucose and several amino acids. Offspring of met dams were smaller during suckling. Gene expression in the lactating mammary glands was impacted to a greater extent by metformin but both metformin and HFD altered genes related to muscle contraction, indicating that these genes may be more susceptible to lactational stressors. Our study demonstrates the impact of common maternal exposures during lactation on milk composition, mammary gland function and offspring growth with metformin having little capacity to recuse from the effects of a maternal HFD during lactation.
Project description:Body mass index and gender influence luminal and mucosa-associated microbiota
| PRJNA401981 | ENA
Project description:: Maternal consumption of artificially sweetened beverages during pregnancy is associated with infant gut microbiota modifications and increased infant body mass index
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.
Project description:Very little is known about miRNAs found in breastmilk cells, which also reflect the cells of the lactating mammary epithelium. Our hypothesis is that breastmilk cells are richer in miRNA compared to other milk fractions, such as skim milk. Further, the effects of milk removal by the infant on milk cell miRNA content and/or composition have not been investigated. Breastmilk cells conserved higher miRNA content than previously published lipid and skim fractions of breastmilk as well as other known sources of miRNA in humans. Specifically, 1,467 known mature miRNAs were identified and a further 1996 novel miRNAs, of which 89 were highly expressed. As previously shown, post-feed milk contained more cells than pre-feed milk, and the same was observed for miRNA content. However, no statistically significant difference was found in the expression of the total known and novel miRNAs between pre- and post-feed milk (p=0.76), although 27 known miRNAs and 1 novel miRNA were higher expressed in post-feed milk. As expected, samples richer in viable cells contained more known miRNAs (p = 0.01). Functional analysis of the top 10 most highly expressed known miRNAs showed that they may be potentially involved in crucial roles for the infant, including body fluid balance, thirst, appetite, immune responses, and development. In conclusion, breastmilk is highly rich in miRNA which may play important functions in the breastfed infant and the lactating breast. Milk removal by the infant can influence the total miRNA content of breastmilk, similar to its cell and fat content, but the miRNA composition remains constant
Project description:Breastfeeding has been associated with long lasting health benefits. Nutrients and bioactive components of human breast milk promote cell growth, immune development, and shield the infant gut from insults and microbial threats. The molecular and cellular events involved in these processes are ill defined. We have established human pediatric enteroids and interrogated maternal milk’s impact on epithelial cell maturation and function in comparison with commercial infant formula. Colostrum applied apically to pediatric enteroid monolayers reduced ion permeability, stimulated epithelial cell differentiation, and enhanced tight junction function by upregulating occludin amount. Breast milk heightened the production of antimicrobial peptide -defensin 5 by goblet and Paneth cells, and modulated cytokine production, which abolished apical release of pro-inflammatory GM-CSF. These attributes were not found in commercial infant formula. Epithelial cells exposed to breast milk elevated apical and intracellular pIgR amount and enabled maternal IgA translocation. Proteomic data revealed a breast milk-induced molecular pattern associated with tissue remodeling and homeostasis. Using a novel ex vivo pediatric enteroid model, we have identified cellular and molecular pathways involved in human milk-mediated improvement of human intestinal physiology and immunity.
Project description:Breast milk is a complex liquid that enriched in immunological components and affect the development of the infant immune system. Exosomes, the membranous vesicles of endocytic origin, are ubiquitously in various body fluids which can mediate intercellular communication. MicroRNAs (miRNAs), a well-defined group of non-coding small RNAs, in human breast milk are packaged inside exosomes. Here, we present the identification of miRNAs in human breast milk exosomes using deep sequencing technology. We found that the immune-related miRNAs are enriched in breast milk exosomes, and are resistant to the general harsh conditions. Four small RNA libraries in human breast milk exosomes from four healthy women (30 +/- 0.9 years old, primiparity) when the infant were aged at 60 days were sequenced.
Project description:The objective of this study was to analyze genome-wide differential methylation patterns in maternal leukocyte DNA in early pregnant and non-pregnant states. This is an age- and body mass index-matched case-control study comparing the methylation patterns of 27,578 cytosine-guanine (CpG) sites in 14,495 genes in maternal leukocyte DNA in early pregnancy (n=14), in the same women postpartum (n=14), and in nulligravid women (n=14) on a BeadChip platform. Transient widespread hypomethylation was found in early pregnancy as compared with the non-pregnant states. Methylation of nine genes was significantly different in early pregnancy compared to both postpartum and nulligravid states (< 10% False Discovery Rate). Early pregnancy may be characterized by widespread hypomethylation compared to non-pregnant states; there is no apparent permanent methylation imprint after a normal-term gestation. Nine potential candidate genes were identified as differentially methylated in early pregnancy and may play a role in the maternal adaptation to pregnancy. This is an age- and body mass index-matched case-control study comparing the methylation patterns of 27,578 cytosine-guanine (CpG) sites in 14,495 genes in maternal leukocyte DNA in early pregnancy (n=14), in the same women postpartum (n=14), and in nulligravid women (n=14) on a BeadChip platform.