Project description:Development of the gut microbiota is greatly impacted in preterm infants. Despite increasing knowledge about microbiota composition in preterm infants, knowledge about the functional signatures of the intestinal microbiota remains limited. The aim was to study transitions in microbiota activity during the first six postnatal weeks in ten preterm infants. A total of 64 stool samples were measured by LC-MS/MS.
Project description:Development of the gut microbiota is greatly impacted in preterm infants. Despite increasing knowledge about microbiota composition in preterm infants, knowledge about the functional signatures of the intestinal microbiota remains limited. The aim was to study transitions in microbiota activity during the first six postnatal weeks in ten preterm infants. A total of 64 stool samples were measured by LC-MS/MS.
Project description:The early changes in innate immunity associated with BPD (bronchopulmonary dysplasia) development are incompletely understood. Transcriptome analyses from cord blood of preterm infants indicate a monocyte-centered, profibrotic signature at birth confirming TNFalpha as a critical upstream regulator for the development of BPD.
Project description:91 preterm infant gut metaproteomes measured in technical duplicate using an eleven salt pulse 2D-LC-MS/MS method. Samples represent 17 preterm infants over the first several weeks of life, of which 6 preterm infants eventually developed necrotizing enterocolitis.
Project description:Preterm birth is often predisposed by chorioamnionitis (CA) and CA affects the fetal gut and lungs via intra-amniotic (IA) inflammation, thus accentuating the proinflammatory effects of preterm birth. It is not known if IA inflammation also affects other perfusion-sensitive organs (e.g., kidneys) before and after preterm birth. Using preterm pigs as model for preterm infants, we hypothesized that CA induces fetal and neonatal renal dysfunctions that can intially be detected via plasma proteome, partly explaining the frequent renal dysfunction in preterm infants. Fetal pigs (88% gestation) were given an IA dose of lipopolysaccharide (LPS, 1 mg/kg, n=28), delivered preterm by cesarean section three days later, and compared with controls (CON, n=26) at birth and postnatal day five. Plasma proteome and protein markers of inflammatory pathways were evaluated.
Project description:We conducted a prospective cohort study with independent Discovery and Validation cohorts, to formulate predictive biomarkers for Bronchopulmonary Dysplasia in extremely preterm infants. Tracheal aspirate samples were collected at birth from extremely preterm infants. Exosomes were extracted from tracheal aspirates and total RNA was extracted from these exosomes from individual samples. miRNA profiling for all ~ 800 miRNAs was conducted on each sample by nanostring platform. This study found that a distinct airway exosomal miRNA sigrature at birth (decreased miR 876-3p) predicts future development of severe Bronchopulmonary Dysplasia in extremely preterm infants.
Project description:Mesenchymal stem cells (MSCs) hold great therapeutic potential in morbidities associated with preterm birth. However, the molecular expressions of hMSCs in preterm birth infants have not been systematically evaluated. In this study, we presented the dual-omics analyses of umbilical cord (UC) derived hMSCs to identify the dysregulated cellular functions. Materials and methods: The UC-MSCs were collected from 10 full-term and 8 preterm birth infants for transcriptomics and proteomics analyses by using microarray and iTRAQ-based proteome profiling. The integrative analysis of dual-omics data discovered 5,615 commonly identified genes/proteins of which 29 genes/proteins showed consistent up- or down-regulation in preterm birth. The Gene Ontology analysis revealed that the biological processes of mitochondrial translation and cellular response to oxidative stress were mainly enriched in 290 differential expression proteins (DEPs) while the 421 differential expression genes (DEGs) were majorly involved in secondary alcohol metabolic process, cellular response to stress, and mitotic cell cycle in preterm birth. Besides, we identified a 13-protein module involving CUL2 and CUL3, which plays an important role in cullin-RING-based ubiquitin ligase complex, as potential mechanism for preterm birth. The dual-omics data not only provided new insights to the molecular mechanism but also to identify panel of candidate markers associated with preterm birth.
Project description:DNA methylation (DNAm) plays a determining role in neural cell fate and provides a molecular link between early life stress and life-course neuropsychiatric disease. Preterm birth is a profound environmental stressor that is closely associated with alterations in connectivity of neural systems and long-term neuropsychiatric impairment. The aims of this study were to examine the relationship between preterm birth and DNAm and to investigate factors that contribute to variance in DNAm. DNA was collected from preterm infants (birth < 32 weeks’ gestation) and healthy controls (birth > 37 weeks), and a genome-wide analysis of DNAm was performed; diffusion MRI (dMRI) data were acquired from the preterm group. The major fasciculi were segmented, and fractional anisotropy, mean diffusivity and tract shape were calculated. Principal components analysis was used to investigate the contribution of MRI features and key clinical variables to variance in DNAm. Differentially methylated regions were found within 25 gene bodies and 61 promoters of protein-coding genes in preterm infants compared with controls; 10 of these are associated with neural development or function. Differences detected in the array were validated with pyrosequencing. Ninety-five percent of the variance in DNAm in preterm infants was explained by 23 principal components (PC); corticospinal tract shape associated with 6th PC, and gender and early nutritional exposure associated with the 7th PC. Preterm birth is associated with alterations in the methylome at sites that influence neural development and function. The differentially methylated regions identified provide several promising candidate genes for understanding the genetic/epigenetic basis of preterm brain injury.
Project description:Genome-wide DNA methylation profiling of DNA extracted from dried blood spots from preterm and term subjects using longitudinal samples collected at birth and 18 years of age. Infinium HM450 arrays were used to measure methylation at 347,789 autosomal CpGs. DNA was analysed from individuals at birth and 18-years and included 12 preterm and 12 term controls. Bisulphite converted DNA from the 48 samples were hybridised to the Illumina Infinium 450K Human Methylation Beadchip