Human lung metagenome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA520924 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8783040_1.fastq.gz | Fastqsanger.gz | |||
| SRR8783040_2.fastq.gz | Fastqsanger.gz | |||
| SRR8783050_1.fastq.gz | Fastqsanger.gz | |||
| SRR8783050_2.fastq.gz | Fastqsanger.gz | |||
| SRR8783060_1.fastq.gz | Fastqsanger.gz |
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Project description:Early life viral infections are responsible for pulmonary exacerbations that can contribute to disease progression in young children with CF. The most common respiratory viruses detected in the CF airway are human rhinoviruses (RV) and susceptibility to infection has been attributed to dysregulated airway epithelial responses, although evidence has been conflicting. Here, we exposed airway epithelial cells from children with and without CF to RV in vitro. Using RNA-Seq, we profiled the transcriptomic differences of CF and non-CF airway epithelial cells at baseline and in response to RV. There were only modest differences between CF and non-CF cells at baseline. In response to RV there were 1442 and 896 differentially expressed genes in CF and non-CF airway epithelial cells respectively. The core antiviral responses in CF and non-CF airway epithelial cells were mediated through interferon signaling although type 1 and 3 interferon proteins were reduced in CF airway epithelial cells following viral challenge consistent with previous reports. The transcriptional responses in CF airway epithelial cells were more complex than in non-CF airway epithelial cells with more over-represented biological pathways ranging from cytokine signaling to metabolic and biosynthetic pathways. Network analysis highlighted that the differentially expressed genes of CF airway epithelial cells transcriptional responses were highly interconnected and formed a more complex network than observed in non-CF airway epithelial cells. These data provide novel insights to the CF airway epithelial cells responses to RV infection and highlight potential pathways that could be targeted to improve antiviral and anti-inflammatory responses in CF.
2020-07-03 | GSE138167 | GEO
Project description:Taxonomic signatures of Cystic Fibrosis airway microbiota
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Project description:Cystic fibrosis (CF) is an inherited, multi-system disease caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, a ubiquitous ion channel important for epithelial hydration. A direct consequence of this dysfunction is impaired mucociliary clearance, chronic airway infection and a persistent neutrophilic inflammatory response that results in progressive loss of lung function, development of respiratory failure and premature death. Partial restoration of CFTR function is now possible for most CF patients through mutation specific CFTR modulators. Ivacaftor monotherapy produces significant clinical improvement in CF patients with the G511D mutation. Dual therapy, combining ivacaftor with lumacaftor or tezacaftor, results in modest clinical improvements in patients homozygous for F508del. More recently, triple therapy with elexacaftor/tezacaftor/ivacaftor (ETI) has led to dramatic improvements in lung function and quality of life in patients homozygous and heterozygous for F508del. Sputum proteomics is a powerful research technique capable of identifying important airway disease mechanisms by interrogating the proteome, an entire set of proteins within biological samples. It has confirmed the central role of neutrophilic immune dysregulation in CF and non-CF bronchiectasis, particularly involving the release of antimicrobial proteins and neutrophil-extracellular traps (NETs), and through impaired anti-inflammatory mechanisms. These processes produce distinct molecular signatures within the sputum proteome that become increasingly abnormal with chronic airway infection and progressive lung disease severity. In CF patients, airway and systemic inflammatory cytokines potentially related to these signatures reduce with the various forms of CFTR modulation. To date, no studies of ETI therapy in CF lung disease have assessed large-scale change in protein expression using untargeted proteomics. We hypothesised that ETI therapy would shift the sputum proteome toward health, potentially normalising airway biology in people with CF. The objectives of this study were to investigate changes in the CF sputum proteome with the introduction of ETI, correlate these with changes in clinical markers of disease severity, and make comparisons with the sputum proteome in healthy controls and in repeat samples from CF patients not suitable for ETI therapy. We also explored which molecular pathways associated with CF lung disease did not change with ETI.
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Project description:Gut microbiome research is rapidly moving towards the functional characterization of the microbiota by means of shotgun meta-omics. Here, we selected a cohort of healthy subjects from an indigenous and monitored Sardinian population to analyze their gut microbiota using both shotgun metagenomics and shotgun metaproteomics. We found a considerable divergence between genetic potential and functional activity of the human healthy gut microbiota, in spite of a quite comparable taxonomic structure revealed by the two approaches. Investigation of inter-individual variability of taxonomic features revealed Bacteroides and Akkermansia as remarkably conserved and variable in abundance within the population, respectively. Firmicutes-driven butyrogenesis (mainly due to Faecalibacterium spp.) was shown to be the functional activity with the higher expression rate and the lower inter-individual variability in the study cohort, highlighting the key importance of the biosynthesis of this microbial by-product for the gut homeostasis. The taxon-specific contribution to functional activities and metabolic tasks was also examined, giving insights into the peculiar role of several gut microbiota members in carbohydrate metabolism (including polysaccharide degradation, glycan transport, glycolysis and short-chain fatty acid production). In conclusion, our results provide useful indications regarding the main functions actively exerted by the gut microbiota members of a healthy human cohort, and support metaproteomics as a valuable approach to investigate the functional role of the gut microbiota in health and disease.
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Project description:<p>Progressive decline in lung function is a hallmark of chronic obstructive pulmonary disease (COPD). Although airway dysbiosis occurs in COPD, whether it contributes to disease progression remains unknown. Here, through a longitudinal analysis on 181 COPD individuals from two large cohorts involving four UK clinical centers, we showed that baseline airway dysbiosis, characterized by enrichment of opportunistic pathogenic taxa, was associated with rapid forced expiratory volume in one second (FEV1) decline over two years. Co-presence of Moraxella, Staphylococcus and Stenotrophomonas was associated with an accelerated FEV1 decline by 139.7 mL/year. The dysbiosis was associated with exacerbation-related FEV1 fall and sudden FEV1 fall at clinical stability, two critical events contributing to long-term FEV1 decline. The microbiota association with FEV1 decline was validated in a third, independent cohort in China. Human multi-omics, murine and cellular mechanistic studies showed that chronic airway colonization of Staphylococcus aureus promoted lung function decline through producing homocysteine, which elicited an apoptosis-to-NETosis shift in neutrophils toward persistent inflammation via AKT1-S100A8/A9 axis. Prophylactic and therapeutic depletion of S. aureus via bacteriophage restored lung function in emphysema mice. These results provide a fresh approach to slow COPD progression by targeting the airway microbiome.</p><p><br></p><p><strong>Linked studies:</strong></p><p><strong>UPLC-MS/MS assays</strong> of human samples are reported in this study.</p><p><strong>UPLC-MS/MS assays</strong> of murine samples are reported in<strong> </strong><a href='https://www.ebi.ac.uk/metabolights/MTBLS6894' rel='noopener noreferrer' target='_blank'><strong>MTBLS6894</strong></a>.</p><p><strong>UPLC-MS/MS assays</strong> of original cohort human samples are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS4017' rel='noopener noreferrer' target='_blank'><strong>MTBLS4017</strong></a>.</p>
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Project description:Lung disease causes most of the morbidity and mortality in cystic fibrosis (CF). However, understanding its pathogenesis has been hindered by lack of an animal model with characteristic features of CF. To overcome this problem, we recently generated pigs with targeted CFTR genes. We now report that within months of birth, CF pigs spontaneously develop hallmark features of CF lung disease including airway inflammation, remodeling, mucus accumulation, and infection. Their lungs contained multiple bacterial species, suggesting an equal opportunity host defense defect. In humans, the temporal and/or causal relationships between inflammation and infection have remained uncertain. To investigate these processes, we studied newborn pigs. Their lungs showed no inflammation, but were less often sterile than controls. Moreover, after intrapulmonary bacterial challenge, CF pigs failed to eradicate bacteria as effectively as wild- type pigs. These results suggest that impaired bacterial elimination is the pathogenic event that initiates a cascade of inflammation and pathology in CF lungs. Finding that CF pigs have a bacterial host defense defect within hours of birth provides an exciting opportunity to further investigate pathogenesis and to test therapeutic and preventive strategies before secondary consequences develop. Pig model of human CF lung disease
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Project description:Microbiota in Upper and Lower Airway in Children Raw sequence reads
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Project description:Cystic fibrosis (CF) is a life-shortening disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Although bacterial lung infection and the resulting inflammation cause most of the morbidity and mortality, how loss of CFTR first disrupts airway host defense has remained uncertain. We asked what abnormality impairs elimination when a bacterium lands on the pristine surface of a newborn CF airway? To investigate this defect, we interrogated the viability of individual bacteria immobilized on solid grids and placed on the airway surface. As a model we studied CF pigs, which spontaneously develop hallmark features of CF lung disease. At birth, their lungs lack infection and inflammation, but have a reduced ability to eradicate bacteria. Here we show that in newborn wild-type pigs, the thin layer of airway surface liquid (ASL) rapidly killed bacteria in vivo, when removed from the lung, and in primary epithelial cultures. Lack of CFTR reduced bacterial killing. We found that ASL pH was more acidic in CF, and reducing pH inhibited the antimicrobial activity of ASL. Reducing ASL pH diminished bacterial killing in wild-type pigs, and increasing ASL pH rescued killing in CF pigs. These results directly link the initial host defense defect to loss of CFTR, an anion channel that facilitates HCO3- transport. Without CFTR, airway epithelial HCO3- secretion is defective, ASL pH falls and inhibits antimicrobial function, and thereby impairs killing of bacteria that enter the newborn lung. These findings suggest that increasing ASL pH might prevent the initial infection in patients with CF and that assaying ASL pH or bacterial killing could report on the benefit of therapeutic interventions. 11 samples of trachea primary airway epithelial cultures representing CFTR+/+ and CFTR-/- pigs. Pig samples representing 14 bronchus and 12 trachea tissue samples submitted in GSE21071.
2012-03-29 | E-GEOD-36906 | biostudies-arrayexpress
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