Project description:Human respiratory syncytial virus (HRSV) is the main cause of bronchiolitis during the first year of life, but other viruses such as rhinovirus also occur and are clinically indistinguishable. In hospitalized infants with bronchiolitis, the analysis of the peripheral blood mononuclear cells (PBMC) gene expression might be useful for identification the etiologies caused by HRSV and human rhinovirus (HRV) and to the development of future tests, as well as to elucidate the pathogenic mechanisms triggered by different viral agents and new therapeutic possibilities. In this study, we conducted a comparative global gene expression analysis of infants with acute viral bronchiolitis infected by HRSV (HRSV group) or HRV (HRV group).
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:On going efforts are directed at understanding the mutualism between the gut microbiota and the host in breast-fed versus formula-fed infants. Due to the lack of tissue biopsies, no investigators have performed a global transcriptional (gene expression) analysis of the developing human intestine in healthy infants. As a result, the crosstalk between the microbiome and the host transcriptome in the developing mucosal-commensal environment has not been determined. In this study, we examined the host intestinal mRNA gene expression and microbial DNA profiles in full term 3 month-old infants exclusively formula fed (FF) (n=6) or breast fed (BF) (n=6) from birth to 3 months. Host mRNA microarray measurements were performed using isolated intact sloughed epithelial cells in stool samples collected at 3 months. Microbial composition from the same stool samples was assessed by metagenomic pyrosequencing. Both the host mRNA expression and bacterial microbiome phylogenetic profiles provided strong feature sets that clearly classified the two groups of babies (FF and BF). To determine the relationship between host epithelial cell gene expression and the bacterial colony profiles, the host transcriptome and functionally profiled microbiome data were analyzed in a multivariate manner. From a functional perspective, analysis of the gut microbiota's metagenome revealed that characteristics associated with virulence differed between the FF and BF babies. Using canonical correlation analysis, evidence of multivariate structure relating eleven host immunity / mucosal defense-related genes and microbiome virulence characteristics was observed. These results, for the first time, provide insight into the integrated responses of the host and microbiome to dietary substrates in the early neonatal period. Our data suggest that systems biology and computational modeling approaches that integrate “-omic” information from the host and the microbiome can identify important mechanistic pathways of intestinal development affecting the gut microbiome in the first few months of life. KEYWORDS: infant, breast-feeding, infant formula, exfoliated cells, transcriptome, metagenome, multivariate analysis, canonical correlation analysis 12 samples, 2 groups
Project description:Background: There is limited data on how different RSV genotypes and associated viral loads influence disease phenotypes. We characterized the genetic variability of RSV strains during five non-consecutive respiratory seasons, and evaluated the role of RSV subtypes, genotypes and viral loads on clinical disease severity. Methods: Healthy infants hospitalized with RSV bronchiolitis were prospectively enrolled and nasopharyngeal samples obtained within 24h of hospitalization for RSV load quantitation by PCR, typing and genotyping. Parameters of disease severity were assessed, and multivariate models constructed to identify virologic and clinical factors predictive of clinical outcomes. Results: From March 2004 to April 2011, we enrolled 253 patients (56.5 % males; median age 2.1 (1.1-4.0) months). RSV A infections predominated over RSV B (69% vs. 31%; p<0.001) and showed greater genotype variability. The most common genotypes were RSV A/GA2, A/GA5 and RSV B/BA. Infants infected with RSV GA5 had higher viral loads compared with GA2 or BA infection (p<0.01), independent of duration of symptoms. After adjusting for other covariates, RSV A/GA5 infections were associated with longer hospital stay. Conclusions: RSV A infections were more frequent than RSV B infections and displayed greater genetic variability. Infections with GA5 were independently associated with clinical disease severity.
Project description:The search for novel biomarkers for respiratory diseases, especially those associated with extreme premature birth, has been a challenge over the past several decades. In this study, we performed a qualitative comparison of proteomic profiles derived from a novel noninvasive sampling methodology, nasopharyngeal aspiration, and an established invasive methodology, tracheal aspiration, in preterm neonates, to determine whether nasopharyngeal aspirates (NPAs) are suitable for respiratory biomarker research. Paired NPA and tracheal aspirate (TA) samples (N=5) were collected from 1-week-old neonates and analyzed via high-throughput proteomics. The shared and specific sample proteins were studied. Shared and sample-specific proteins were analyzed using state-of-the-art enrichment analyses to evaluate lung tissue specificity and proteomic similarity.
Project description:The impact of prematurity in human development and neonatal diseases, such as bronchopulmonary dysplasia, have been widely reported. However, little is known about the effects of prematurity on the programs of stem cell self-renewal and differentiation of the upper respiratory epithelium, key for adaptation to neonatal life. Here we developed a minimally invasive methodology for isolation and functional analysis of basal cells from nasopharyngeal (NP) aspirates of newborn infants in organotypic cultures to address this issue. We show that pre-term NP progenitors have a markedly distinct molecular signature of a prematurity-associated abnormal program of proliferation and mitochondria quality control compared to term cells. Prematurity differentially inhibited mitochondria respiration and, although it did not prevent cell differentiation it was later associated with differences in mitochondrial and innate immunity-related genes. Together these differences suggested increased sensitivity of pre-term progenitors to environmental stressors compared to term under non-homeostatic conditions.
2021-01-07 | GSE164358 | GEO
Project description:Nasopharyngeal microbiome in SARS-CoV-2 infected women and infants
| PRJNA1078389 | ENA
Project description:Gut, oral and nasopharyngeal microbiota dynamics in the clinical course of hospitalized infants with respiratory syncytial virus bronchiolitis