Maternal diet shapes infant microbiota and defensive capacity against infections in early life via differential breast milk composition
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PROVIDER: PRJEB67941 | ENA |
REPOSITORIES: ENA
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2023-08-13 | PXD039923 | Pride
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2025-01-22 | MSV000096907 | MassIVE
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.
2024-08-27 | GSE273780 | GEO
Project description:Human breast milk (HBM) is the “gold standard” for infant nutrition. When breast milk is insufficient or unavailable, infant milk formula (IMF) can provide a safe and nutritious alternative. However, IMFs often differ considerably from HBM in composition, particularly fatty acid profiles, and health function. Here, we compared the digestibility and potential health functions of IMF containing low cream (LC-) or high cream (HC-) content compared to pooled HBM. After simulated infant digestion of these samples, bioavailability of key nutrients and immunomodulatory activities were determined via cell-based in-vitro assays. A Caenorhabditis elegans (C.elegans) leaky gut model was also established to investigate effects on gut health. Distinct differences were observed in higher diversity of peptides released from HC-IMF when compared to LC-IMF during simulated digestion. Higher levels of free fatty acids were absorbed through 21-day differentiated Caco-2/HT-29MTX monolayers from HC-IMF, when compared to LC-IMF and HBM. Furthermore, the immune-modulating properties of HC-IMF appeared to be more in line with HBM than LC-IMF, as observed by comparable secretion of IL-10 and IL-1β from THP-1 cells following exposure. HC-IMF also supported significantly faster intestinal recovery following distortion, vs. LC-IMF in C.elegans. These initial observations suggest that increasing the cream content in infant milk formulation may provide added nutritional and functional benefits which are closer to that of HBM.
2025-05-06 | PXD043255 | Pride
Project description:Respiratory defensive behaviors, like coughing, play a crucial role in protecting the respiratory system, ensuring its integrity and optimal function. How these critical behaviors are regulated by sensory stimuli within the body remains largely unknown. Here, we show that the nucleus of the solitary tract (NTS) in mice, a key hub in the brain for processing internal sensory signals and mediating interoceptive processes, contains heterogenous neuronal populations that differentially control breathing. Within these subtypes, activation of tachykinin 1 (Tac1) neurons triggers a specific respiratory behavior. Our detailed characterization of respiratory defensive behaviors reveals that these responses are cough-like behaviors. Chemogenetic silencing or genetic ablation of Tac1 neurons significantly reduces cough-like behaviors induced by tussive challenges. These Tac1 neurons receive synaptic inputs from the bronchopulmonary chemosensory and mechanosensory neurons in the vagal ganglion, and directly integrate the medullary regions to control sequential phases of cough-like defensive behaviors. We propose that these Tac1 neurons are a key component of the airway-vagal-brain neural circuit that controls cough-like defensive behaviors in mice, and they coordinate the downstream modular circuits to elicit the sequential motor pattern of forceful expiratory responses.
2024-06-05 | GSE268741 | GEO
Project description:Infant Immune Responses to Early Life Vaccinations
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Project description:Infant Immune Responses to Early Life Vaccinations
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Project description:Over the course of milk digestion, native milk proteases and infant digestive proteases fragment intact proteins into peptides with potential bioactivity. This study investigated the release of peptides over three hours of gastric digestion in 14 preterm infant sample sets. The peptide content was extracted and analyzed from milk and gastric samples via Orbitrap tandem mass spectrometry. The relative ion intensity (abundance) and count of peptides in each sample were compared over time and between infants fed milk fortified with bovine milk fortifier and infants fed unfortified milk. Bioactivity of the identified peptides was predicted by sequence homology to known bioactive milk peptides. Both total and bioactive peptide abundance and count continuously increased over three hours of gastric digestion. After accounting for infant weight, length, and post-conceptual age, fortification of milk limited the release of peptides from human milk proteins. Peptides that survived further gastric digestion after their initial release were structurally more similar to bioactive peptides than non-surviving peptides. This work is the first to provide a comprehensive profile of milk peptides released during gastric digestion over time, which is an essential step in determining which peptides are most likely to be biologically relevant in the infant.
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