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:To investigate potential drivers of respiratory disease in survivors of preterm birth by examining the transcriptomic profile of airway epithelial cells at approximately one year of age. Nasal airway epithelial brushings were collected, and primary cell cultures established from 8 term (GA>37w, 3.0 ± 1.1 years at collection) and 11 preterm participants (GA 25-31.2 weeks, 1.4 ± 0.1 years at collection). RNA was extracted from cultured cells and bulk RNA sequencing performed on both the ex vivo and in vitro samples.
Project description:In this study, the molecular signature of placenta membrane from preterm birth placenta was assessed and compared to full-term placenta by proteomic profiling with the aim to identify molecules relevant to preterm birth.
Project description:Intestinal microbiota colonization is important for intestinal development and health of preterm infants, especially those with extremely low birth weight. Recent studies indicated for a dynamic crosstalk between that gut microbiota and DNA methylome of host intestinal cells. Thereby, we sought to determine the epigenomic and metagenomic consequences of suppression of microbiota colonization in the intestine of preterm neonates to gain insights into biological pathways that shape the interface between the gut microbiota and the preterm intestinal cells. We examined 14 preterm piglets by comparing the conventional preterm neonates with those ones treated with oral antibiotics for genome wide DNA methylation and 16S rDNA microbiome. Our results demonstrated an extensive genome-wide DNA methylation changes in response to the suppression of intestinal microbe colonization, especially genes involved in neonatal immune response signaling and glycol-metabolism pathways were identified. Our study highlights several key genes that might predispose preterm neonates to NEC risk due to their key roles involved in the immune-metabolic networks. Our study not only provided rich omic-data to interpret molecular program in relation with microbiota-associated methylome-proteome network changes, but also confer clinical usage of key gene markers for potential early diagnostics of NEC of preterm neonates.
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:Extreme preterm infants are a growing population in the neonatal intensive care unit. Multiple factors play a role in preterm birth, resulting in complications including severe bronchopulmonary dysplasia (sBPD) without or with and pulmonary hypertension (BPD-PH). The goal of this study was to identify biomarker signatures associated with sBPD and BPD-PH. We analyzed profiles in tracheal aspirates (TAs) from 46 extremely preterm infants receiving invasive mechanical ventilation (25 sBPD, 21 BPD-PH) . We found specific miRNA signatures in TAs that may serve as biomarkers for the two disease phenotypes.
Project description:<p>The pregnancy vaginal microbiome contributes to risk of preterm birth, the primary cause of death in children under 5 years of age. Here we describe direct on-swab metabolic profiling by Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) for sample preparation-free characterisation of the cervicovaginal metabolome in two independent pregnancy cohorts (VMET, n = 160; 455 swabs; VMET II, n = 205; 573 swabs). By integrating metataxonomics and immune profiling data from matched samples, we show that specific metabolome signatures can be used to robustly predict simultaneously both the composition of the vaginal microbiome and host inflammatory status. In these patients, vaginal microbiota instability and innate immune activation, as predicted using DESI-MS, associated with preterm birth, including in women receiving cervical cerclage for preterm birth prevention. These findings highlight direct on-swab metabolic profiling by DESI-MS as an innovative approach for preterm birth risk stratification through rapid assessment of vaginal microbiota-host dynamics.</p><p><br></p><p><strong>Linked cross omic data sets:</strong></p><p>Meta-taxonomics data associated with this study are available in the European Nucleotide Archive (ENA): accession number <a href='https://www.ebi.ac.uk/ena/browser/view/PRJEB11895' rel='noopener noreferrer' target='_blank'>PRJEB11895</a>, <a href='https://www.ebi.ac.uk/ena/browser/view/PRJEB12577' rel='noopener noreferrer' target='_blank'>PRJEB12577</a> and <a href='https://www.ebi.ac.uk/ena/browser/view/PRJEB41427' rel='noopener noreferrer' target='_blank'>PRJEB41427</a>.</p>
2021-09-23 | MTBLS717 | MetaboLights
Project description:Oral microbiome in preterm birth
Project description:Extreme preterm infants are a growing population in neonatal intensive care units who carry a high mortality and morbidity. Multiple factors play a role in preterm birth, resulting in major impact on organogenesis leading to complications including bronchopulmonary dysplasia (BPD). The goal of this study was to identify biomarker signatures associated with BPD severity. We analyzed profiles in tracheal aspirates (TAs) from 25 extremely preterm infants receiving invasive mechanical ventilation. Eight infants were diagnosed with mild/moderate BPD, and 17 were diagnosed with severe BPD, according to the NHLBI consensus conference classification . We found specific miRNA signatures in TAs that may serve as biomarkers for BPD severity.