In infants with severe bronchiolitis: dual-transcriptomic profiling of nasopharyngeal microbiome and host response.
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ABSTRACT:
SUBMITTER: Fujiogi M
PROVIDER: S-EPMC7335686 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
Publications
In infants with severe bronchiolitis: dual-transcriptomic profiling of nasopharyngeal microbiome and host response.
Fujiogi Michimasa M Camargo Carlos A CA Bernot James P JP Freishtat Robert J RJ Harmon Brennan B Mansbach Jonathan M JM Castro-Nallar Eduardo E Perez-Losada Marcos M Hasegawa Kohei K
Pediatric research 20200106 2
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Project description:Bronchiolitis is a leading cause of infant hospitalizations but its immunopathology remains poorly understood. Here we present data from 244 infants hospitalized with bronchiolitis in a multicenter prospective study, assessing the host response (transcriptome), microbial composition, and microbial function (metatranscriptome) in the nasopharyngeal airway, and associate them with disease severity. We investigate individual associations with disease severity identify host response, microbial taxonomical, and microbial functional modules by network analyses. We also determine the integrated relationship of these modules with severity. Several modules are significantly associated with risks of positive pressure ventilation use, including the host-type I interferon, neutrophil/interleukin-1, T cell regulation, microbial-branched-chain amino acid metabolism, and nicotinamide adenine dinucleotide hydrogen modules. Taken together, we show complex interplays between host and microbiome, and their contribution to disease severity.
| S-EPMC9427849 | biostudies-literature
Project description:BackgroundSevere bronchiolitis (ie, bronchiolitis requiring hospitalization) during infancy is a major risk factor for childhood asthma. However, the exact mechanism linking these common conditions remains unclear.ObjectivesThis study sought to examine the integrated role of airway microbiome (both taxonomy and function) and host response in asthma development in this high-risk population.MethodsThis multicenter prospective cohort study of 244 infants with severe bronchiolitis (median age, 3 months) examined the infants' nasopharyngeal metatranscriptomes (microbiomes) and transcriptomes (hosts), as well as metabolomes at hospitalization. The longitudinal relationships investigated include (1) major bacterial species (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis), (2) microbial function, and (3) host response with risks of developing asthma by age 6 years.ResultsFirst, the abundance of S pneumoniae was associated with greater risks of asthma (P = .01), particularly in infants with nonrhinovirus infection (Pinteraction = .04). Second, of 328 microbial functional pathways that are differentially enriched by asthma development, the top pathways (eg, fatty acid and glycolysis pathways; false discovery rate [FDR] < 1 × 10-12) were driven by these 3 major species (eg, positive association of S pneumoniae with glycolysis; FDR < 0.001). These microbial functional pathways were validated with the parallel metabolome data. Third, 104 transcriptome pathways were differentially enriched (FDR < .05)-for example, downregulated interferon-α and -γ and upregulated T-cell activation pathways. S pneumoniae was associated with most differentially expressed transcripts (eg, DAGLB; FDR < 0.05).ConclusionsBy applying metatranscriptomic, transcriptomic, and metabolomic approaches to a multicenter cohort of infants with bronchiolitis, this study found an interplay between major bacterial species, their function, and host response in the airway, and their longitudinal relationship with asthma development.
| S-EPMC9547815 | biostudies-literature
Project description:RationaleBronchiolitis is the most common lower respiratory infection in infants; however, it remains unclear which infants with bronchiolitis will develop severe illness. In addition, although emerging evidence indicates associations of the upper-airway microbiome with bronchiolitis severity, little is known about the mechanisms linking airway microbes and host response to disease severity.ObjectivesTo determine the relations among the nasopharyngeal airway metabolome profiles, microbiome profiles, and severity in infants with bronchiolitis.MethodsWe conducted a multicenter prospective cohort study of infants (age <1 yr) hospitalized with bronchiolitis. By applying metabolomic and metagenomic (16S ribosomal RNA gene and whole-genome shotgun sequencing) approaches to 144 nasopharyngeal airway samples collected within 24 hours of hospitalization, we determined metabolome and microbiome profiles and their association with higher severity, defined by the use of positive pressure ventilation (i.e., continuous positive airway pressure and/or intubation).Measurements and main resultsNasopharyngeal airway metabolome profiles significantly differed by bronchiolitis severity (P < 0.001). Among 254 metabolites identified, a panel of 25 metabolites showed high sensitivity (84%) and specificity (86%) in predicting the use of positive pressure ventilation. The intensity of these metabolites was correlated with relative abundance of Streptococcus pneumoniae. In the pathway analysis, sphingolipid metabolism was the most significantly enriched subpathway in infants with positive pressure ventilation use compared with those without (P < 0.001). Enrichment of sphingolipid metabolites was positively correlated with the relative abundance of S. pneumoniae.ConclusionsAlthough further validation is needed, our multiomic analyses demonstrate the potential of metabolomics to predict bronchiolitis severity and better understand microbe-host interaction.
| S-EPMC5649976 | biostudies-literature
Project description:Little is known about the relationship between the specific airway microbiota composition and severity of bronchiolitis. We aimed to identify nasopharyngeal microbiota profiles and link these profiles to acute severity in infants hospitalised for bronchiolitis.We conducted a multicentre prospective cohort study of 1005 infants (age <1 year) hospitalised for bronchiolitis over three winters, 2011-2014. By applying a 16S rRNA gene sequence and clustering approach to the nasopharyngeal aspirates collected within 24 h of hospitalisation, we determined nasopharyngeal microbiota profiles and their association with bronchiolitis severity. The primary outcome was intensive care use, i.e. admission to an intensive care unit or use of mechanical ventilation.We identified four nasopharyngeal microbiota profiles: three profiles were dominated by one of Haemophilus, Moraxella or Streptococcus, while the fourth profile had the highest bacterial richness. The rate of intensive care use was highest in infants with a Haemophilus-dominant profile and lowest in those with a Moraxella-dominant profile (20.2% versus 12.3%; unadjusted OR 1.81, 95% CI 1.07-3.11, p=0.03). After adjusting for 11 patient-level confounders, the rate remained significantly higher in infants with Haemophilus-dominant profiles (OR 1.98, 95% CI 1.08-3.62, p=0.03). These findings were externally validated in a separate cohort of 307 children hospitalised for bronchiolitis.
| S-EPMC5459592 | biostudies-literature
Project description: Not available
| S-EPMC6105518 | biostudies-literature
Project description: Not available
| S-EPMC7960557 | biostudies-literature
Project description:ObjectivesTo detect RSV or other thirteen respiratory viruses as possible causer agent of bronchiolitis in infants.MethodThis is an epidemiological analytical study, conducted using a nasopharyngeal aspirate of 173 hospitalized children younger than two years old with severe bronchiolitis in three hospitals in the Campinas Metropolitan Region (CMR) during 2013-14. The data was statically evaluated by Pearson's chi-squared test with statistical significance of 0.05 and 95% confidence level.ResultsAs expected, the most prevalent viruses detected were RSV A and B in 47% and 16% of the samples, respectively. However, almost a third of severe bronchiolitis cases there were no detection of RSV, and the viruses more commonly detected were rhinoviruses, which were identified in almost a quarter of all positive samples for at least a viral agent.ConclusionsAlthough nothing could be concluded from the disease severity and clinical-epidemiological data, the present study's results indicate that severe bronchiolitis is not always related to RSV infections in children younger than two years old, and the rhinoviruses were more prevalent in these cases. These findings reinforce the need to carry out a viral diagnosis in the hospital emergency would be very appropriate for all cases of respiratory infections in children, even for diseases in which the primary etiological agent seems to be well known.
| S-EPMC9432127 | biostudies-literature
Project description: Not available
| S-EPMC5385272 | biostudies-literature
Project description:BackgroundBronchiolitis is associated with a greater risk of developing recurrent wheezing, but with currently available tools, it is impossible to know which infants with bronchiolitis will develop this condition. This preliminary prospective study aimed to assess whether urine metabolomic analysis can be used to identify children with bronchiolitis who are at risk of developing recurrent wheezing.MethodsFifty-two infants <1 year old treated in the emergency department at University Hospital of Padova for acute bronchiolitis were enrolled (77% tested positive for respiratory syncytial virus [RSV]). Follow-up visits were conducted for 2 years after the episode of bronchiolitis. Untargeted metabolomic analyses based on mass spectrometry were performed on urine samples collected from infants with acute bronchiolitis. Data modeling was based on univariate and multivariate data analyses.ResultsWe distinguished children with and those without postbronchiolitis recurrent wheeze, defined as ≥3 episodes of physician-diagnosed wheezing. Pathway overrepresentation analysis pointed to a major involvement of the citric acid cycle (P < .001) and some amino acids (lysine, cysteine, and methionine; P ≤ .015) in differentiating between these 2 groups of children.ConclusionThis is the first study showing that metabolomic profiling of urine specimens from infants with bronchiolitis can be used to identify children at increased risk of developing recurrent wheezing.
| S-EPMC7107429 | biostudies-literature
Project description:BackgroundSevere bronchiolitis (i.e. bronchiolitis requiring hospitalisation) during infancy is a major risk factor for childhood asthma. However, the exact mechanism linking these common conditions remains unclear. We examined the longitudinal relationship between nasal airway miRNAs during severe bronchiolitis and the risk of developing asthma.MethodsIn a 17-centre prospective cohort study of infants with severe bronchiolitis, we sequenced their nasal microRNA at hospitalisation. First, we identified differentially expressed microRNAs (DEmiRNAs) associated with the risk of developing asthma by age 6 years. Second, we characterised the DEmiRNAs based on their association with asthma-related clinical features, and expression level by tissue and cell types. Third, we conducted pathway and network analyses by integrating DEmiRNAs and their mRNA targets. Finally, we investigated the association of DEmiRNAs and nasal cytokines.ResultsIn 575 infants (median age 3 months), we identified 23 DEmiRNAs associated with asthma development (e.g. hsa-miR-29a-3p; false discovery rate (FDR) <0.10), particularly in infants with respiratory syncytial virus infection (FDR for the interaction <0.05). These DEmiRNAs were associated with 16 asthma-related clinical features (FDR <0.05), e.g. infant eczema and corticosteroid use during hospitalisation. In addition, these DEmiRNAs were highly expressed in lung tissue and immune cells (e.g. T-helper cells, neutrophils). Third, DEmiRNAs were negatively correlated with their mRNA targets (e.g. hsa-miR-324-3p/IL13), which were enriched in asthma-related pathways (FDR <0.05), e.g. toll-like receptor, PI3K-Akt and FcɛR signalling pathways, and validated by cytokine data.ConclusionIn a multicentre cohort of infants with severe bronchiolitis, we identified nasal miRNAs during illness that were associated with major asthma-related clinical features, immune response, and risk of asthma development.
| S-EPMC10578345 | biostudies-literature