Microbiota development in late-preterm infants
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB19937 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR1879440.fastq.gz | Fastqsanger.gz | |||
| ERR1879450.fastq.gz | Fastqsanger.gz | |||
| ERR1879460.fastq.gz | Fastqsanger.gz | |||
| ERR1879470.fastq.gz | Fastqsanger.gz | |||
| ERR1879480.fastq.gz | Fastqsanger.gz |
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Project description:Host immune responses during late-onset sepsis (LOS) in very preterm infants are poorly characterised due to a complex and dynamic pathophysiology and challenges in working with small available blood volumes. We present here an unbiased transcriptomic analysis of whole peripheral blood from very preterm infants at the time of LOS. RNA-Seq was performed on peripheral blood samples (6 – 29 days postnatal age) taken at the time of suspected LOS from very preterm infants <30 weeks gestational age. Infants were classified based on blood culture positivity and elevated C-reactive protein concentrations as having confirmed LOS (n=5), possible LOS (n=4) or no LOS (n=9). Bioinformatics and statistical analyses performed included pathway over-representation and protein-protein interaction network analyses. Plasma cytokine immunoassays were performed to validate differentially expressed cytokine pathways.The blood leukocyte transcriptional responses of infants with confirmed LOS differed significantly from infants without LOS (1,317 differentially expressed genes). However, infants with possible LOS could not be distinguished from infants with no LOS or confirmed LOS. Transcriptional alterations associated with LOS included genes involved in pathogen recognition (mainly TLR pathways), cytokine signalling (both pro-inflammatory and inhibitory responses), immune and haematological regulation (including cell death pathways), and metabolism (altered cholesterol biosynthesis). At the transcriptional-level cytokine responses during LOS were characterised by over-representation of IFN-α/β, IFN-γ, IL-1 and IL-6 signalling pathways and up-regulation of genes for inflammatory responses. Infants with confirmed LOS had significantly higher levels of IL-1α and IL-6 in their plasma. Blood responses in very preterm infants with LOS are characterised by altered host immune responses that appear to reflect unbalanced immuno-metabolic homeostasis.
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Project description:We procured peripheral whole blood from ten healthy preterm infants and ten preterm infants with bronchopulmonary dysplasia
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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.
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Project description:Introduction: Early pulmonary vascular disease in preterm infants is associated with the subsequent development of bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH), however, mechanisms that contribute to or identify infants with increased susceptibility for BPD and/or PH are incompletely understood. Therefore, we tested if changes in circulating angiogenic peptides during the first week of life are associated with the later development of BPD and/or PH. We further sought to determine alternate peptides and related signalling pathways with the risk for BPD or PH. Methods: We prospectively enrolled infants with gestational age <34 weeks gestation and collected blood samples during their first week of life. BPD and PH were assessed at 36 weeks postmenstrual age. Samples were assayed for each of the 1121 peptides included in the SOMAscanTM technology, with subsequent pathway analysis. Results: Of 102 study infants, 82 had BPD and 13 had PH. Multiple angiogenic proteins (PF-4, VEGF121, ANG-1, BMP10, HGF, ANG2) were associated with the subsequent diagnosis of BPD, and FGF-19, PF-4, CTAP-III and PDGF-AA levels were associated with BPD severity. Early increases in BMP10 was strongly associated with the late risk for BPD and PH. Conclusion: We found that early alterations of circulating angiogenic peptides and others were associated with the subsequent development of BPD. We further identified peptides that were associated with BPD severity and BPD-associated PH, including BMP10. We speculate that proteomic biomarkers during the first week of life may identify infants at risk for BPD and/or PH to enhance care and research.
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Project description:Bronchopulmonary dysplasia (BPD) is a lung disease in premature infants characterized by impaired pulmonary development which persists into later life. While advances in neonatal care have improved survival rates of premature infants, cases of BPD haves been increased. Therapeutic options are limited for prevention and treatment. This study was designed to explore the relationship between gestational age (GA), birth weight and estímate blood cell-type composition in premature infants and to elucidate early epigenetic biomarkers associated with BPD. Peripheral blood DNA (at days 14 and 28) from preterm neonates that went on to develop BPD (n = 14) or not (nonBPD, n = 93) was applied to Illumina EPIC methylation arrays. Using DNA methylation analysis of cord blood DNA, we investigated association of GA and birth weight with the estimated distribution of cord blood cell types, particularly the nucleated red blood cell (NRBC) in a pilot-size cohort of preterm infants with or without BPD. We describe changes in methylation-based estimates of blood cell-type composition in relation to GA and birth weight. After adjusting for covariates (GA, birth weight, cell type proportions, etc.) we identify differentially methylated CpGs and genes associated with BPD at different time points.
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