Metagenomisc_lung
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB28158 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR2732360.fastq.gz | Fastqsanger.gz | |||
| ERR2732370.fastq.gz | Fastqsanger.gz | |||
| ERR2732380.fastq.gz | Fastqsanger.gz | |||
| ERR2732390.fastq.gz | Fastqsanger.gz | |||
| ERR2732400.fastq.gz | Fastqsanger.gz |
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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.
2023-11-14 | PXD041950 | Pride
Project description:Memory helper T cells provide long-lasting host defeMemory helper T cells provide long-lasting host defense against microbial pathogens, while distinct subpopulations of memory T cells drive chronic inflammatory diseases such as asthma. Asthma is a chronic allergic inflammatory disease with airway remodeling including fibrotic changes. The immunological mechanisms that induce airway fibrotic changes in allergic inflammation remain unknown. We found that Interleukin-33 (IL-33) enhanced Amphiregulin production by the IL-33 receptor, ST2hi memory T helper-2 (Th2) cells. Amphiregulin-epidermal growth factor receptor (EGFR)-mediated signaling directly reprogramed eosinophils to an inflammatory state with enhanced production of Osteopontin, a key profibrotic immunomodulatory protein. IL-5-producing memory Th2 cells and Amphiregulin-producing memory Th2 cells appeared to cooperate to establish lung fibrosis. The analysis of polyps from patients with eosinophilic chronic rhinosinusitis revealed fibrosis with accumulation of Amphiregulin-producing CRTH2hiCD161hiCD45RO+CD4+ Th2 cells and Osteopontin-producing eosinophils. Thus, the IL-33-Amphiregulin-Osteopontin axis directs fibrotic responses in eosinophilic airway inflammation and is a potential target for the treatment of fibrosis induced by chronic allergic disorders. against microbial pathogens, while distinct subpopulations of memory T cells drive chronic inflammatory diseases such as asthma. Asthma is a chronic allergic inflammatory disease with airway remodeling including fibrotic changes. The immunological mechanisms that induce airway fibrotic changes in allergic inflammation remain unknown. We found that Interleukin-33 (IL-33) enhanced Amphiregulin production by the IL-33 receptor, ST2 hi memory T helper-2 (Th2) cells. Amphiregulin-epidermal growth factor receptor (EGFR)-mediated signaling directly reprogramed eosinophils to an inflammatory state with enhanced production of Osteopontin, a key profibrotic immunomodulatory protein. IL-5-producing memory Th2 cells and Amphiregulin-producing memory Th2 cells appeared to cooperate to establish lung fibrosis. The analysis of polyps from patients with eosinophilic chronic rhinosinusitis revealed fibrosis with accumulation of Amphiregulin-producing CRTH2hiCD161hiCD45RO+CD4+ Th2 cells and Osteopontin-producing eosinophils. Thus, the IL-33-Amphiregulin-Osteopontin axis directs fibrotic responses in eosinophilic airway inflammation and is a potential target for the treatment of fibrosis induced by chronic allergic disorders.
2018-08-21 | GSE114921 | GEO
Project description:Background: Chronic obstructive pulmonary disease (COPD) is a serious chronic disease of the airways that affects many people worldwide and have limited treatment options. While small animal models provide a platform for therapeutic investigations into COPD, their deficiencies continue to impede clinical translation. Alternatively, as a large animal model, sheep have a respiratory system anatomically and physiologically similar to that of humans, encouraging their use in airway disease research. The aim of this study was to better understand disease pathology in a large animal (sheep) experimental model of COPD. Methods: COPD was induced in sheep following lung exposure to porcine elastase (PE) and repeated weekly lung exposures to lipopolysaccharide (LPS) over a period of 8 weeks. Bronchoalveolar fluid and blood samples were collected for immune analyses. Lung function was assessed and lung tissues were collected for histopathology and RNA sequencing. Results: Lung neutrophil levels were elevated in response to repeated airway exposure to PE/LPS, accompanied by a significant decline in ventilation over time. Histological evidence of COPD-like disease changes included chronic inflammation with increased airway and tissue inflammation scores, together with significantly larger airway wall area measures, increased connective tissue deposition and dysregulated gene expression. Conclusions: These studies demonstrate sustained chronic airway inflammation and pathophysiological lung changes in a sheep model of COPD, providing many similarities to that seen in COPD patients. This work opens a pathway for future translational studies using this unique large animal model of COPD, which will serve to bridge the gap between smaller animal models and humans.
2023-12-31 | GSE242416 | GEO
Project description:Pseudomonas aeruginosa is an environmentally resilient bacterium and an important cause of both acute and chronic infections in people with impaired natural barriers or immunological defences. Chronic respiratory infection with P. aeruginosa is a major cause of morbidity and mortality in people with airway diseases, including cystic fibrosis and bronchiectasis. Chronic airway infection is characterised by periods of relative stability punctuated by pulmonary exacerbations, during which times rapid bacterial outgrowth necessitates intense antimicrobial chemotherapy. The periods of stable infection can be modelled in mice, by nasal instillation of airway-adapted P. aeruginosa in saline, leading to prolonged colonisation of both upper airway (sinus) and lower airway (lung) environments that is not associated with symptomatic disease. Here, we use NMR metabolomics to investigate the impact of P. aeruginosa colonisation on the metabolic landscape of sinuses and lungs. Lung infection led to pronounced changes in the airway metabolome, with depletion of glucose and myo-inositol but enrichment of glutathione, relative to uninfected lungs. Changes in the sinuses were more subtle but could be identified through dimensionality reduction approaches. The NMR spectral peaks which discriminated between infected and uninfected sinuses in partial least squares discriminant analysis included those for lactate and choline but were mostly representative of yet unidentified metabolites. These data highlight the differential impact of infection on separate airway compartments and identify undefined metabolites undergoing pronounced abundance changes during infection.
2025-11-06 | MTBLS6052 | MetaboLights
Project description:The epithelial layer lining the airways has a central role in maintaining lung health, particularly serving as a barrier to prevent infection and delivery of harmful particles, which are cleared from the lung on the mucociliary escalator driven by the epithelium. Robust methods to culture primary airway epithelial cells were developed several decades ago and these cells provide the model of choice to investigate many diseases of the human lung. However, to date the molecular signature of cells from different regions of the airway epithelium has not been well characterized. Here we examine primary cells derived from human tracheal and bronchial tissues and perform genome-wide analysis of their active regulatory elements and gene expression profiles. We also compare cells from healthy and diseased (cystic fibrosis) donor lung tissue. Our data reveal an airway cell signature that is divergent from other epithelial cell types and from immortalized or transformed airway epithelial cell lines. The differences between tracheal and bronchial cells are clearly evident as are common regulatory features between the cell types of two different origins. Only minor variation is seen between cells from healthy or CF bronchial cells. These data are a valuable resource for functional genomics analysis of airway epithelial tissues in human health and disease.
2018-02-28 | GSE101993 | GEO
Project description:Background: Healthy individuals exposed to low levels of cigarette smoke have a decrement in lung function and higher risk for lung disease compared to unexposed individuals. We hypothesized that healthy individuals exposed to low levels of tobacco smoke must have biologic changes in the small airway epithelium compared to healthy unexposed individuals. Methods: Small airway epithelium was obtained by bronchoscopy from 121 individuals; microarrays assessed genome wide gene expression, and urine nicotine and cotinine were used to categorized subjects as “nonsmokers,” “active smokers,” and “low exposure.” The gene expression data was used to determine the threshold and ID50 of urine nicotine and cotinine at which the small airway epithelium showed abnormal responses. Results: There was no threshold of urine nicotine without an abnormal small airway epithelial response, and only a slightly above detectable threshold abnormal response for cotinine. The nicotine ID50 for nicotine was 25 ng/ml and cotinine 104 ng/ml. Conclusions: The small airway epithelium detects and responds to low levels of tobacco smoke with transcriptome modifications. This provides biologic correlates of epidemiologic studies linking low level tobacco smoke exposure to lung health risk, health, identifies genes in the lung cells most sensitive to tobacco smoke and defines thresholds at the lung epithelium responds to inhaled tobacco smoke. Affymetrix arrays were used to assess the gene expression data of smoking-responsive genes in the in small airway epithelium obtained by fiberoptic bronchoscopy of 48 healthy non-smokers (non-smoker or Nsaets), 65 healthy smokers (smoker), 7 symptomatic smokers (SYMs) and a healthy occasional smoker (OcSs). YSB and LO contributed equally to the study.
2011-02-02 | E-GEOD-19667 | biostudies-arrayexpress
Project description:Supersulphides (inorganic and organic sulphides with sulphur catenation) manifest diverse physiological functions. These supersulphides are mainly generated from mitochondrial cysteinyl-tRNA synthetase (CARS2) that functions as a principal cysteine persulphide synthase (CPERS). Here we found powerful protective functions of supersulphides in viral airway infections (influenza and COVID-19) and chronic lung diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and aged lungs. Enhanced supersulphide exhalation also occurred from human airways in COVID-19 as well as the hamster model of SARS-CoV-2 infection, as identified by breath supersulphur-omics that we developed herein. The lung damage related to oxidative stress and inflammation in mouse models of COPD, IPF, and ageing and the lethal effects that resulted were mitigated by endogenous supersulphides, supplied via CARS2/CPERS or exogenously by the supersulphide donor glutathione trisulphide. Our findings thus elucidated the airway protective role of supersulphides and their therapeutic potential in viral and chronic lung diseases.
2023-07-14 | PXD043607 | Pride
Project description:Bronchopulmonary dysplasia (BPD) is a chronic lung disease of prematurity. Exposure to noxious stimuli such as hyperoxia, volutrauma, and infection in infancy can have long-reaching impacts on lung health and predispose towards the development of conditions such as chronic obstructive pulmonary disease (COPD) in adulthood. BPD and COPD are both marked by lung tissue degradation, neutrophil influx, and decreased lung function. Both diseases also express a change in microbial signature characterized by firmicute depletion. However, the relationship between pulmonary bacteria and the mechanisms of downstream disease development has yet to be elucidated. We hypothesized that murine models of BPD would show heightened acetylated proline-glycine-proline (Ac-PGP) pathway and neutrophil activity, and through gain- and loss-of-function studies we show that Ac-PGP plays a critical role in driving BPD development. We further test a inhaled live biotherapeutic (LBP) using active Lactobacillus strains in in vitro and in vivo models of BPD and COPD. The Lactobacillus-based LBP is effective in improving lung structure and function, mitigating neutrophil influx, and reducing a broad swath of pro-inflammatory markers in these models of chronic pulmonary disease via the MMP-9/PGP (matrix metalloproteinase/proline-glycine-proline) pathway. Inhaled LBPs show promise in addressing common pathways of disease progression that in the future can be targeted in a variety of chronic lung diseases.
2024-07-08 | GSE271605 | GEO
Project description:Airway basal stem cells (BSCs) in chronic lung diseases accumulate memories to promote disease-specific pathogenesis. Whether acute lung infection also endows BSCs with an inflammatory memory to impair epithelial regeneration is unknown. Here, we derived multiple BSC lines from patients with and without COVID-19 (CoV19) using tracheal aspirate (TA) as a viable source of bronchial BSCs. While tested negative for SARS-CoV-2, BSC lines from CoV19 patients bore a proinflammatory gene signature, exhibited early cell cycle exist, and displayed goblet cell hypoplasia following differentiation in air-liquid interface (ALI). These phenotypes reproduced, at least partially, changes in BSCs in patients with CoV19 assessed by bioinformatic analysis of preexisting single cell transcriptomes of BSCs and by staining of lung sections for select markers. Such a memory in BSCs previously exposed to CoV19 was mediated by increases in chromosomal accessibility at key inflammatory gene loci associated with gene dysregulation and sustained STAT3 activation. Blockade of STAT3 hyperactivation in CoV19-exposed BSCs restored mucociliary differentiation in ALI. Taken together, BSCs acquire an epigenetic memory of CoV19 to impair epithelial regeneration. BSC derivation from TA provides a versatile approach to model airway epithelium in health and lung diseases.
2023-06-01 | GSE212410 | GEO