Maternal adiposity alters the human milk metabolome: a link between non-glucose monosaccharides and infant adiposity
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
TISSUE(S): Breast
DISEASE(S): Obesity
PROVIDER: ST001322 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| mwtab | Other |
Items per page: 5 1 - 1 of 1 |
Similar Datasets
Project description:Human milk is the optimal nutrition source for infants, and oligosaccharides represent the third most abundant component in milk after lactose and fat. Human milk oligosaccharides (HMO) are favorable macromolecules which are, interestingly, indigestible by the infant but serve as substrates for bacteria. Hypothesizing that the maternal diet itself might influence HMO composition, we sought to directly determine the effect maternal diet on HMO and the milk bacteria. Employing a human cross-over study design, we demonstrate that distinct maternal dietary carbohydrate and energy sources preferentially alter milk concentrations of HMO, including fucosylated species. We find significant associations between the concentration of HMO-bound fucose and the abundance of fucosidase (a bacterial gene that digests fucose moieties) harbored by milk bacteria. These studies reveal a successive mechanism by which the maternal diet during lactation alters milk HMO composition, which in turn shapes the functional milk microbiome prior to infant ingestion.
| S-EPMC7745035 | biostudies-literature
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.
| S-EPMC6599743 | biostudies-literature
Project description:Breast milk delivers nutrition and protection to the developing infant. There has been considerable research on the high-molecular-weight milk components; however, low-molecular-weight metabolites have received less attention. To determine the effect of maternal phenotype and diet on the human milk metabolome, milk collected at day 90 postpartum from 52 healthy women was analyzed by using proton nuclear magnetic resonance spectroscopy. Sixty-five milk metabolites were quantified (mono-, di-, and oligosaccharides; amino acids and derivatives; energy metabolites; fatty acids and associated metabolites; vitamins, nucleotides, and derivatives; and others). The biological variation, represented as the percentage CV of each metabolite, varied widely (4-120%), with several metabolites having low variation (<20%), including lactose, urea, glutamate, myo-inositol, and creatinine. Principal components analysis identified 2 clear groups of participants who were differentiable on the basis of milk oligosaccharide concentration and who were classified as secretors or nonsecretors of fucosyltransferase 2 (FUT2) gene products according to the concentration of 2'-fucosyllactose, lactodifucotetraose, and lacto-N-fucopentaose I. Exploration of the interrelations between the milk sugars by using Spearman rank correlations revealed significant positive and negative associations, including positive correlations between fucose and products of the FUT2 gene and negative correlations between fucose and products of the fucosyltransferase 3 (FUT3) gene. The total concentration of milk oligosaccharides was conserved among participants (%CV = 18%), suggesting tight regulation of total oligosaccharide production; however, concentrations of specific oligosaccharides varied widely between participants (%CV = 30.4-84.3%). The variability in certain milk metabolites suggests possible roles in infant or infant gut microbial development. This trial was registered at clinicaltrials.gov as NCT01817127.
| S-EPMC4083237 | biostudies-literature
Project description:Human milk is a dynamic biofluid, and its detailed composition receives increasing attention. While most studies focus on changes over time or differences between maternal characteristics, interindividual variation receives little attention. Nevertheless, a comprehensive insight into this can help interpret human milk studies and help human milk banks provide targeted milk for recipients. This study aimed to map interindividual variation in the human milk proteome, peptidome, and metabolome and to investigate possible explanations for this variation. A set of 286 milk samples was collected from 29 mothers in the third month postpartum. Samples were pooled per mother, and proteins, peptides, and metabolites were analyzed. A substantial coefficient of variation (>100%) was observed for 4.6% and 36.2% of the proteins and peptides, respectively. In addition, using weighted correlation network analysis (WGCNA), 5 protein and 11 peptide clusters were obtained, showing distinct characteristics. With this, several associations were found between the different data sets and with specific sample characteristics. This study provides insight into the dynamics of human milk protein, peptide, and metabolite composition. In addition, it will support future studies that evaluate the effect size of a parameter of interest by enabling a comparison with natural variability.
| S-EPMC8981310 | biostudies-literature
Project description:Cancer survivors experience numerous treatment side effects that negatively affect their quality of life. Cognitive side effects are especially insidious, as they affect memory, cognition, and learning. Neurocognitive deficits occur prior to cancer treatment, arising even before cancer diagnosis, and we refer to them as "tumor brain." Metabolomics is a new area of research that focuses on metabolome profiles and provides important mechanistic insights into various human diseases, including cancer, neurodegenerative diseases, and aging. Many neurological diseases and conditions affect metabolic processes in the brain. However, the tumor brain metabolome has never been analyzed. In our study we used direct flow injection/mass spectrometry (DI-MS) analysis to establish the effects of the growth of lung cancer, pancreatic cancer, and sarcoma on the brain metabolome of TumorGraft™ mice. We found that the growth of malignant non-CNS tumors impacted metabolic processes in the brain, affecting protein biosynthesis, and amino acid and sphingolipid metabolism. The observed metabolic changes were similar to those reported for neurodegenerative diseases and brain aging, and may have potential mechanistic value for future analysis of the tumor brain phenomenon.
| S-EPMC5826252 | biostudies-literature
Project description:ScopeHuman milk (HM) is rich in bioactive compounds and essential nutrients. While research has focused on lipids, minerals, immune markers, microbiota, and oligosaccharides, specific metabolites are less studied. This study uses targeted metabolomics to identify and quantify metabolites in HM and explores the impact of perinatal and dietary factors on the metabolomic profile.Methods and resultsIn a cross-sectional study of 123 healthy lactating women, HM samples were collected up to 1 month postpartum and analyzed using the Biocrates MxP Quant 500 kit. Maternal and neonatal clinical, anthropometric, and nutritional data were collected. A total of 432 metabolites were quantified and categorized into 20 groups. The metabolomic profiles formed three distinct clusters, primarily driven by triglyceride concentration differences. Docosahexaenoic acid (DHA) levels were higher in HM from mothers with vaginal delivery compared to C-section births and differences in hexoses were found between exclusive and mixed-feeding practices. Maternal diets rich in lipids and animal proteins were associated with elevated amino acids, sphingolipids, and glycosyl-ceramides.ConclusionThe HM metabolome was grouped into three clusters influenced by delivery mode, lactation practices, and maternal diet. This comprehensive analysis opens new avenues to explore HM composition and offers valuable insights for future dietary interventions aimed at modulating HM.
| S-EPMC11670290 | biostudies-literature
Project description:Introduction: The functional role of milk for the developing neonate is an area of great interest, and a significant amount of research has been done. However, a lot of work remains to fully understand the complexities of milk, and the variations imposed through genetics. It has previously been shown that both secretor (Se) and Lewis blood type (Le) status impacts the human milk oligosaccharide (HMO) content of human milk. While some studies have compared the non-HMO milk metabolome of Se+ and Se- women, none have reported on the non-HMO milk metabolome of Se- and Le- mothers. Method and Results: To determine the differences in the non-HMO milk metabolome between Se-Le- mothers and other HMO phenotypes (Se+Le+, Se+Le-, and Se-Le+), 10 milk samples from 10 lactating mothers were analyzed using nuclear magnetic resonance (NMR) spectroscopy. Se or Le HMO phenotypes were assigned based on the presence and absence of 6 HMOs generated by the Se and Le genes. After classification, 58 milk metabolites were compared among the HMO phenotypes. Principal component analysis (PCA) identified clear separation between Se-Le- milk and the other milks. Fold change analysis demonstrated that the Se-Le- milk had major differences in free fatty acids, free amino acids, and metabolites related to energy metabolism. Conclusion: The results of this brief research report suggest that the milk metabolome of mothers with the Se-Le- phenotype differs in its non-HMO metabolite composition from mothers with other HMO phenotypes.
| S-EPMC7901958 | biostudies-literature
Project description:Human milk (HM) appetite hormones and macronutrients may mediate satiety in breastfed infants. This study investigated associations between maternal adiposity and concentrations of HM leptin, adiponectin, protein and lactose, and whether these concentrations and the relationship between body mass index and percentage fat mass (%FM) in a breastfeeding population change over the first year of lactation. Lactating women (n = 59) provided milk samples (n = 283) at the 2nd, 5th, 9th and/or 12th month of lactation. Concentrations of leptin, adiponectin, total protein and lactose were measured. Maternal %FM was measured using bioimpedance spectroscopy. Higher maternal %FM was associated with higher leptin concentrations in both whole (0.006 ± 0.002 ng/mL, p = 0.008) and skim HM (0.005 ± 0.002 ng/mL, p = 0.007), and protein (0.16 ± 0.07 g/L, p = 0.028) concentrations. Adiponectin and lactose concentrations were not associated with %FM (0.01 ± 0.06 ng/mL, p = 0.81; 0.08 ± 0.11 g/L, p = 0.48, respectively). Whole milk concentrations of adiponectin and leptin did not differ significantly over the first year of lactation. These findings suggest that the level of maternal adiposity during lactation may influence the early appetite programming of breastfed infants by modulating concentrations of HM components.
| S-EPMC5372915 | biostudies-literature
Project description:(1) Background: Pregnancy presents a challenge to maternal glucose homeostasis; suboptimal adaptations can lead to gestational diabetes mellitus (GDM). Human milk oligosaccharides (HMOs) circulate in maternal blood in pregnancy and are altered with GDM, suggesting influence of glucose homeostasis on HMOs. We thus assessed the HMO response to glucose load during an oral glucose tolerance test (OGTT) and investigated HMO associations with glucose tolerance/insulin sensitivity in healthy pregnant women. (2) Methods: Serum of 99 women, collected at 0 h, 1 h and 2 h during a 75 g OGTT at 24-28 gestational weeks was analyzed for HMOs (2'FL, 3'SLN, LDFT, 3'SL) by HPLC; plasma glucose, insulin and C-peptide were analyzed by standard biochemistry methods. (3) Results: Serum 3'SL concentrations significantly increased from fasting to 1 h after glucose load, while concentrations of the other HMOs were unaltered. Higher 3'SL at all OGTT time points was associated with a generally more diabetogenic profile, with higher hepatic insulin resistance (HOMA-IR), lower insulin sensitivity (Matsuda index) and higher insulin secretion (C-peptide index 1). (4) Conclusions: Rapid increase in serum 3'SL post-oral glucose load (fasted-fed transition) indicates utilization of plasma glucose, potentially for sialylation of lactose. Associations of sialylated HMOs with a more diabetogenic profile suggest sustained adaptations to impaired glucose homeostasis in pregnancy. Underlying mechanisms or potential consequences of observed HMO changes remain to be elucidated.
| S-EPMC10534497 | biostudies-literature
Project description:BackgroundMaternal exposure to environmental chemicals during pregnancy can influence various maternal and offspring health parameters. Modification of maternal metabolism by environmental exposure may be an important pathway for these impacts. However, there is limited evidence regarding exposure to a wide array of chemicals and the metabolome during pregnancy.ObjectivesWe investigated the relationship between the urinary exposome and metabolome during pregnancy.MethodsUrine samples were collected in the first and third trimesters from 1,024 pregnant women recruited in prenatal clinics in Jiangsu Province, China. The exposome was analyzed using the first trimester sample with ultra-high performance liquid chromatography-high resolution accurate mass spectrometry (UHPLC-HRMS) and inductively coupled plasma mass spectrometry. The metabolome was analyzed using the third trimester sample with UHPLC-HRMS. We evaluated associations between each of 106 exposures in the first trimester with 139 metabolites in the third trimester.ResultsWe identified 1,245 significant associations (p<3.39×10-6, Bonferroni correction) between chemical exposures and maternal metabolism during pregnancy. Among elements, the largest number of the significant metabolic associations were observed for magnesium, and among organic compounds, for 4-tert-octylphenol. We used exposome-metabolome associations to explore mechanisms underlying published associations between prenatal chemical exposures and offspring health outcomes. This integration of the literature with our results suggests that reported associations between 10 analytes and birth weight, gestational age, fat deposition, neurobehavioral development, immunological disorders, and hypertension may be partially mediated by metabolites associated with these exposures.DiscussionThis high-dimensional analysis of the urinary exposome and metabolome identified many associations between chemical exposures and maternal metabolism during pregnancy. Integration of these associations with the literature on health outcomes of exposure suggests that environmental modulation of the maternal metabolome may play a role in the association between prenatal exposure on pregnancy and child health outcomes. https://doi.org/10.1289/EHP9745.
| S-EPMC8901044 | biostudies-literature