The Lung Microbiome in Rheumatoid Arthritis and Autoimmunity
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ABSTRACT:
ORGANISM(S): human lung metagenome
PROVIDER: GSE84608 | GEO | 2017/01/31
SECONDARY ACCESSION(S): PRJNA330624
REPOSITORIES: GEO
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Project description:We examined 36 biopsies taken from digital dermatitis lesions of Holstein cows. The target was the V3 -V4 variable region of 16S rRNA using Treponema specific primers. We identified 20 different taxa of Treponema using this approach. Phylogenetic study of the Treponema taxa found in digital dermatitis lesions of Holstein cows.
2013-06-25 | E-GEOD-42426 | biostudies-arrayexpress
Project description:Introduction: Sarcoidosis is a multisystem immuno-inflammatory disorder of unknown etiology that most commonly involves the lungs. We hypothesized that an unbiased approach to identify pathways activated in alveolar macrophagesâa key immuno-inflammatory cell in the lungâcan shed light on the pathogenesis of this complex disease. Methods: We recruited 15 patients with various stages of sarcoidosis and 12 healthy controls. All subjects underwent bronchoscopy with lavage. For each subject, total RNA was extracted from bronchoalveolar (BAL) cells and hybridized to an Affymetrix GeneChip Human Genome U133A 2.0 microarray. Rigorous statistical methods were applied to identify differential gene expression between subjects with sarcoidosis vs. controls. To better elucidate pathways differentially activated between these groups, we applied gene set enrichment analysis (GSEA) to the transcriptional profiles of BAL cells. We used false discovery rate (FDR) < 0.01 to designate significant enrichment. Results: Sarcoid patients were either non-smokers or ex-smokers, all had lung involvement and only 2 were on systemic prednisone. Healthy controls were all non-smokers. Comparison of BAL cell gene expression between sarcoidosis and healthy subjects revealed over 1200 differentially expressed genes at an FDR cutoff < 0.01. Several previously described immune mediators, such as interferon gamma, were up-regulated in the sarcoidosis subjects. Since genes often exert their influence through functionally coherent modules, we performed GSEA based on global expression profiles of alveolar macrophages between the subject groups. We identified more than 200 gene sets enriched in patients with sarcoidosis whereas very few pathways were over-represented in the healthy controls. Many of the sarcoidosis-associated pathways mapped to inflammatory and immune-related processes including T-cell signaling, graft vs. host disease, IL-12, IL-23, and IL-17 pathways, and oxidative phosphorylation. However, we also found and confirmed significant alteration in Proteasome-related pathways. Conclusions: BAL cells in sarcoidosis are characterized by enrichment of distinct transcriptional networks involved in immuno-inflammatory and proteasomal processes. Our findings add to the growing evidence implicating airspace resident cells in the pathogenesis of sarcoidoisis and identify specific pathways whose activation may modulate disease progression. Total RNA from BAL cells of 15 subjects with sarcoidosis and 12 healthy controls was hybridized to 27 Affymetrix Genechip Human U133A 2.0 microarrays
2016-07-22 | E-GEOD-75023 | biostudies-arrayexpress
Project description:Background: We got interested whether genes of airway basal cells are enriched in sarcoidosis. Methods: Bronchoscopy with bronchoalveolar lavage (BAL) was performed in 26 patients with sarcoidosis, chest-x-ray type III and IV, and 20 healthy donors and isolated BAL cells.Transcriptome of BAL cells were studied by using Affymetrix Human Affymetrix Whole-Transcript Human Gene 1.0 ST array on an Affymetrix platform. Microarray data were imported, log2-transformed and quantile normalized using robust multi-array average (RMA). We tested enrichment for airway basal cells by global enrichment analysis. Results: we did not find enrichment of airway basal cell genes in sarcoidosis compared to healthy volunteers.
2018-12-31 | GSE73394 | GEO
Project description:<p><b>Background</b>: The lung microbiome of healthy individuals frequently harbors oral organisms. Despite evidence that micro-aspiration is commonly associated with smoking-related lung diseases, the effects of lung microbiome enrichment with upper airway taxa on inflammation has not been studied. We hypothesize that the presence of oral microorganisms in the lung microbiome is associated with enhanced pulmonary inflammation.</p> <p><b>Methods</b>: We sampled bronchoalveolar lavage (BAL) from the lower airways of 29 asymptomatic subjects (9 never-smokers, 14 former-smokers and 6 current-smokers). We quantified, amplified, and sequenced 16S rRNA genes from BAL samples by qPCR and 454 sequencing. Pulmonary inflammation was assessed by exhaled nitric oxide (eNO), BAL lymphocytes and neutrophils.</p> <p><b>Results</b>: BAL had lower total 16S than supraglottic samples and higher than saline background. Bacterial communities in the lower airway clustered in two distinct groups that we designated as pneumotypes. The rRNA gene concentration and microbial community of the first pneumotype was similar to that of the saline background. The second pneumotype had higher rRNA gene concentration and higher relative abundance of supraglottic-characteristic taxa (SCT), such as Veillonella and Prevotella, and we called it pneumotypeSCT. Smoking had no effect on pneumotype allocation, alpha or beta diversity. PneumotypeSCT was associated with higher BAL lymphocyte-count (p = 0.007), BAL neutrophil-count (p = 0.034) and eNO (p = 0.022).</p> <p><b>Conclusion</b>: A pneumotype with high relative abundance of supraglottic-characteristic taxa is associated with enhanced subclinical lung inflammation. </p>
| phs000633 | dbGaP
Project description:Whole genome mRNA and microRNA profiling of bronchoalveolar lavage (BAL) and peripheral blood mononuclear cell (PBMC) in Sarcoidosis patients
2020-12-08 | GSE109516 | GEO
Project description:In a prior report, we observed two distinct lung microbiomes in healthy subjects that we termed â??pneumotypesâ??: pneumotypeSPT, characterized by high bacterial load and supraglottic predominant taxa (SPT) such as the anaerobes Prevotella and Veillonella; and pneumotypeBPT, with low bacterial burden and background predominant taxa (BPT) found in the saline lavage and bronchoscope. Here, we determined the prevalence of these two contrasting lung microbiome types, in a multi-center study of healthy subjects. We confirmed that a lower airway microbiome enriched with upper airway microbes (pneumotypeSPT) was present in ~45% of healthy individuals. Cross-sectional Multicenter cohort. BAL of 49 healthy subjects from three cohort had their lower airway microbiome assessed by 16S rDNA sequencing and microbial gene content (metagenome) was computationally inferred from taxonomic assignments. The amplicons from total 100 samples are barcoded; the barcode and other clinical characteristics (e.g. inflammatory biomarkers and metabolome data) for each sample are provided in the 'Pneumotype.sep.Map.A1.txt' file.
2016-03-29 | E-GEOD-74395 | biostudies-arrayexpress
Project description:We examined 36 biopsies taken from digital dermatitis lesions of Holstein cows. The target was the V3 -V4 variable region of 16S rRNA using Treponema specific primers. We identified 20 different taxa of Treponema using this approach.
2013-06-25 | GSE42426 | GEO
Project description:Introduction: Sarcoidosis is a multisystem immuno-inflammatory disorder of unknown etiology that most commonly involves the lungs. We hypothesized that an unbiased approach to identify pathways activated in alveolar macrophages—a key immuno-inflammatory cell in the lung—can shed light on the pathogenesis of this complex disease. Methods: We recruited 15 patients with various stages of sarcoidosis and 12 healthy controls. All subjects underwent bronchoscopy with lavage. For each subject, total RNA was extracted from bronchoalveolar (BAL) cells and hybridized to an Affymetrix GeneChip Human Genome U133A 2.0 microarray. Rigorous statistical methods were applied to identify differential gene expression between subjects with sarcoidosis vs. controls. To better elucidate pathways differentially activated between these groups, we applied gene set enrichment analysis (GSEA) to the transcriptional profiles of BAL cells. We used false discovery rate (FDR) < 0.01 to designate significant enrichment. Results: Sarcoid patients were either non-smokers or ex-smokers, all had lung involvement and only 2 were on systemic prednisone. Healthy controls were all non-smokers. Comparison of BAL cell gene expression between sarcoidosis and healthy subjects revealed over 1200 differentially expressed genes at an FDR cutoff < 0.01. Several previously described immune mediators, such as interferon gamma, were up-regulated in the sarcoidosis subjects. Since genes often exert their influence through functionally coherent modules, we performed GSEA based on global expression profiles of alveolar macrophages between the subject groups. We identified more than 200 gene sets enriched in patients with sarcoidosis whereas very few pathways were over-represented in the healthy controls. Many of the sarcoidosis-associated pathways mapped to inflammatory and immune-related processes including T-cell signaling, graft vs. host disease, IL-12, IL-23, and IL-17 pathways, and oxidative phosphorylation. However, we also found and confirmed significant alteration in Proteasome-related pathways. Conclusions: BAL cells in sarcoidosis are characterized by enrichment of distinct transcriptional networks involved in immuno-inflammatory and proteasomal processes. Our findings add to the growing evidence implicating airspace resident cells in the pathogenesis of sarcoidoisis and identify specific pathways whose activation may modulate disease progression.
2016-07-22 | GSE75023 | GEO
Project description:Sarcoidosis is a disease that affects multiple organ systems, with lung disease seen commonly and is the most frequent cause of sarcoidosis-related mortality. We investigated to compare protein expression in the lung from both bronchoalveolar lavage fluid (BAL) cells and fluid (BALF) in newly diagnosed patients with sarcoidosis. Mass spectral data acquisition was conducted on an Orbitrap Fusion instrument in data-dependent mode using either label-free (BALF) or label-based (intracellular) approach. We identified 4,306 high confidence intracellular proteins (probability >99%) with 272 differentially expressed proteins controlling for an FDR 5%. The protein map to several known canonical pathways including phagosome maturation, clathrin-mediated endocytic signaling, NRF-2 mediated oxidant stress response, The examination of BALF identified 1,192 proteins, xxx and xxx protein with differential expression between controls vs. sarcoidosis and progressive vs. non-progressive sarcoidosis respectively. Several of the proteins identified mapping to the differentially expressed proteins were also detected in the BALF.
2021-09-08 | PXD014438 | Pride
Project description:The goal of this study was to investigate and correlate differential methylation and expression in cells from the target organ in non-infectious granulomatous lung diseases, specifically sarcoidosis and chronic beryllium disease (CBD). To that end, cells were collected from patients via bronchoalveolar lavage (BAL), and extracted nucleic acids were hybridized to genome-wide arrays. We conclude that there are many genes that are both differentially methylated and expressed in the BAL fluid of patients with granulomatous lung disease. We identified 2,726 differentially methylated CpGs mapping to 1,944 unique genes when comparing CBD patients to beryllium-sensitized (BeS) individuals without disease. 69% of these genes were also differentially expressed in CBD. Sarcoidosis patients exhibited directional consistency at many loci, but genome-wide significance was not achieved, likely due to heterogeneity in the patient population.
2018-12-05 | GSE110779 | GEO