Biology subjects

Demerath, E. W.

Publications and source records attributed to Demerath, E. W..

5 recordsLinked to original sources

bioRxiv2026

Maternal diet and genetics shape the human milk metabolome

Human milk contains a diverse array of metabolites that contribute to infant nutrition, immune development, and microbial colonization. The maternal factors shaping the milk metabolome, and the relative contribution of genetics or diet vs. other factors, remain poorly understood. Here, we profiled 458 milk metabolites in 349 one-month postpartum human milk samples and integrated metabolomic data with maternal diet, clinical, transcriptomic, and genomic measurements. Maternal diet was broadly associated with milk metabolite composition, with significant correlations identified between dietary features and 323 metabolites. Coffee consumption strongly predicted milk quinic acid and 1,3-dimethyluric acid abundance, while high-fiber dietary patterns were associated with metabolites including proline-betaine and N-acetylornithine. Integration of milk transcriptomic and metabolomic data via machine learning identified biologically plausible gene-metabolite pairs, including associations between QPRT expression and quinolinic acid, and DPEP1 and cysteine-glycine dipeptide. Genome-wide association analyses identified nine study-wide significant metabolite quantitative trait loci, including novel milk-specific associations near PDE6A affecting purine metabolites and near GNE affecting free sialic acid. Comparison with plasma metabolite studies demonstrated both shared and milk-specific genetic regulation of metabolites. Finally, we found that of all tested maternal features, diet explained the largest proportion of variation in the milk metabolome. Together, these findings demonstrate that the human milk metabolome reflects both maternal exposures and mammary gland-specific biology. This work establishes a framework for understanding how genetic and environmental factors shape milk composition.

genomics↗

bioRxiv2024

Assembly, stability, and dynamics of the infant gut microbiome are linked to bacterial strains and functions in mother's milk

The establishment of the gut microbiome in early life is critical for healthy infant development. Although human milk is recommended as sole nutrition for the infant, little is known about how variation in the milk microbiome shapes the microbial communities in the infant gut. Here, we quantified the similarity between the maternal milk and the infant gut microbiome using 507 metagenomic samples collected from 195 mother-infant pairs at one, three, and six months postpartum. Microbial taxonomic overlap between milk and the infant gut was driven by Bifidobacterium longum, and infant microbiomes dominated by B. longum showed greater temporal stability than those dominated by other species. We identified numerous instances of strain sharing between milk and the infant gut, involving both commensal (e.g. B. longum) and pathobiont species (e.g. K. pneumoniae). Shared strains also included typically oral species such as S. salivarius and V. parvula, suggesting possible transmission from the infants oral cavity to the mothers milk. At one month, the infant gut microbiome was enriched in biosynthetic pathways, suggesting that early colonisers might be more metabolically independent than later ones. Lastly, we observed significant overlap in antimicrobial resistance gene carriage within mother-infant pairs. Together, our results suggest that the human milk microbiome has an important role in the assembly, composition, and stability of the infant gut microbiome.

microbiology↗

bioRxiv2023

Human Cytomegalovirus in breast milk is associated with milk composition, the infant gut microbiome, and infant growth

Human cytomegalovirus (CMV) is a highly prevalent herpesvirus that is often transmitted to the neonate via breast milk. Postnatal CMV transmission can have negative health consequences for preterm and immunocompromised infants, but any effects on healthy term infants are thought to be benign. Furthermore, the impact of CMV on the composition of the hundreds of bioactive factors in human milk has not been tested. Here, we utilize a cohort of exclusively breastfeeding full term mother-infant pairs to test for differences in the milk transcriptome and metabolome associated with CMV, and the impact of CMV in breast milk on the infant gut microbiome and infant growth. We find upregulation of the indoleamine 2,3-dioxygenase (IDO) tryptophan-to-kynurenine metabolic pathway in CMV+ milk samples, and that CMV+ milk is associated with decreased Bifidobacterium in the infant gut. Our data indicate a complex relationship between milk CMV, milk kynurenine, and infant growth; with kynurenine positively correlated, and CMV viral load negatively correlated, with infant weight-for-length at 1 month of age. These results suggest CMV transmission, CMV-related changes in milk composition, or both may be modulators of full term infant development.

genomics↗

bioRxiv2023

Human milk variation is shaped by maternal genetics and impacts the infant gut microbiome

Human milk is a complex mix of nutritional and bioactive components that provide complete nutrition for the infant. However, we lack a systematic knowledge of the factors shaping milk composition and how milk variation influences infant health. Here, we used multi-omic profiling to characterize interactions between maternal genetics, milk gene expression, milk composition, and the infant fecal microbiome in 242 exclusively breastfeeding mother-infant pairs. We identified 487 genetic loci associated with milk gene expression unique to the lactating mammary gland, including loci that impacted breast cancer risk and human milk oligosaccharide concentration. Integrative analyses uncovered connections between milk gene expression and infant gut microbiome, including an association between the expression of inflammation-related genes with IL-6 concentration in milk and the abundance of Bifidobacteria in the infant gut. Our results show how an improved understanding of the genetics and genomics of human milk connects lactation biology with maternal and infant health.

genomics↗

bioRxiv2022

Epigenome-wide meta-analysis of BMI in nine population-based cohorts: examining the utility of methylation as a biomarker of BMI

This study sought to examine the association between DNA methylation and body mass index (BMI) and the potential utility of these cytosine-phosphate-guanine (CpG) sites in predicting metabolic health. We pooled summary statistics from six trans-ethnic EWAS of BMI representing nine cohorts (n=17058), replicated these findings in the Womens Health Initiative (WHI, n=4822) and developed an epigenetic prediction score of BMI. In the pooled EWAS, 1265 CpG sites were associated with BMI (p<1E-7), and 1238 replicated in the WHI (FDR < 0.05). We performed several stratified analyses to examine whether these associations differed between individuals of European descent and individuals of African descent. We found five CpG sites had a significant interaction with BMI by race/ethnicity. To examine the utility of the significant CpG sites in predicting BMI, we used elastic net regression to predict log normalized BMI in the WHI (80% training/20% testing). This model found 397 sites could explain 32% of the variance in BMI in the WHI test set. Individuals whose methylome-predicted BMI overestimated their BMI (high epigenetic BMI) had significantly higher glucose and triglycerides, and lower HDL-cholesterol and LDL-cholesterol compared to accurately predicted BMI. Individuals whose methylome-predicted BMI underestimated their BMI (low epigenetic BMI) had significantly higher HDL-cholesterol and lower glucose and triglycerides. This study identified 553 previously identified and 685 novel CpG sites associated with BMI. Participants with high epigenetic BMI had poorer metabolic health suggesting that the overestimation may be driven in part by cardiometabolic derangements characteristic of metabolic syndrome.

genetics↗