Chronic lung allograft dysfunction (CLAD) is the leading cause of death after lung transplant, and azithromycin has variable efficacy in CLAD. The lung microbiome is a risk factor for developing CLAD, but the relationship between lung dysbiosis, pulmonary inflammation, and allograft dysfunction remains poorly understood. Whether lung microbiota predict outcomes or modify treatment response CLAD is unknown.
View Article and Find Full Text PDFThe airway microbiome has the potential to shape chronic obstructive pulmonary disease (COPD) pathogenesis, but its relationship to outcomes in milder disease is unestablished. To identify sputum microbiome characteristics associated with markers of COPD in participants of the Subpopulations and Intermediate Outcome Measures of COPD Study (SPIROMICS). Sputum DNA from 877 participants was analyzed using 16S ribosomal RNA gene sequencing.
View Article and Find Full Text PDFSummary: Here, we introduce SNIKT, a command-line tool for sequence-independent visual confirmation and input-assisted removal of adapter contamination in whole-genome shotgun or metagenomic shotgun long-read sequencing DNA or RNA data.
Availability And Implementation: SNIKT is implemented in R and is compatible with Unix-like platforms. The source code, along with documentation, is freely available under an MIT license at https://github.
Metagenomics holds potential to improve clinical diagnostics of infectious diseases, but DNA from clinical specimens is often dominated by host-derived sequences. To address this, researchers employ host-depletion methods. Laboratory-based host-depletion methods, however, are costly in terms of time and effort, while computational host-depletion methods rely on memory-intensive reference index databases and struggle to accurately classify noisy sequence data.
View Article and Find Full Text PDFChronic obstructive pulmonary disease (COPD) is variable in its development. Lung microbiota and metabolites collectively may impact COPD pathophysiology, but relationships to clinical outcomes in milder disease are unclear. Identify components of the lung microbiome and metabolome collectively associated with clinical markers in milder stage COPD.
View Article and Find Full Text PDFBackground: Aetiology detection is crucial in the diagnosis and treatment of ventilator-associated pneumonia (VAP). However, the detection method needs improvement. In this study, we used Nanopore sequencing to build a quick detection protocol and compared the efficiency of different methods for detecting 7 VAP pathogens.
View Article and Find Full Text PDFWe present SquiggleNet, the first deep-learning model that can classify nanopore reads directly from their electrical signals. SquiggleNet operates faster than DNA passes through the pore, allowing real-time classification and read ejection. Using 1 s of sequencing data, the classifier achieves significantly higher accuracy than base calling followed by sequence alignment.
View Article and Find Full Text PDFHere, we report the complete genome sequences of two strains of Pseudomonas lundensis, M101 and M105, which were isolated from 1% pasteurized milk. Long-read sequencing was performed using a MinION sequencer, and reads were assembled into circular chromosomes of 4,842,187 bp and 4,814,486 bp for M101 and M105, respectively. Both strains had additional plasmid sequences.
View Article and Find Full Text PDFAm J Physiol Lung Cell Mol Physiol
August 2021
We report an improved, nearly closed, high-quality draft genome reconstruction of the Candida albicans CHN1 strain (ATCC MYA-4779), a human isolate, using Illumina and Nanopore sequencing. Covering six complete and two partial nuclear chromosomes along with a partial mitochondrial genome, this assembly is 14,787,852 bases in size, with 5,935 genes.
View Article and Find Full Text PDFNPJ Biofilms Microbiomes
February 2021
Chronic obstructive pulmonary disease (COPD) is heterogeneous in development, progression, and phenotypes. Little is known about the lung microbiome, sampled by bronchoscopy, in milder COPD and its relationships to clinical features that reflect disease heterogeneity (lung function, symptom burden, and functional impairment). Using bronchoalveolar lavage fluid collected from 181 never-smokers and ever-smokers with or without COPD (GOLD 0-2) enrolled in the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS), we find that lung bacterial composition associates with several clinical features, in particular bronchodilator responsiveness, peak expiratory flow rate, and forced expiratory flow rate between 25 and 75% of FVC (FEF).
View Article and Find Full Text PDFBackground: Alterations in the respiratory microbiome are common in chronic lung diseases, correlate with decreased lung function, and have been associated with disease progression. The clinical significance of changes in the respiratory microbiome after lung transplant, specifically those related to development of chronic lung allograft dysfunction (CLAD), are unknown. The aim of this study was to evaluate the effect of lung microbiome characteristics in healthy lung transplant recipients on subsequent CLAD-free survival.
View Article and Find Full Text PDFInhaled oxygen, although commonly administered to patients with respiratory disease, causes severe lung injury in animals and is associated with poor clinical outcomes in humans. The relationship between hyperoxia, lung and gut microbiota, and lung injury is unknown. Here, we show that hyperoxia conferred a selective relative growth advantage on oxygen-tolerant respiratory microbial species (e.
View Article and Find Full Text PDFThe bacterial microbiome of human body sites, previously considered sterile, remains highly controversial because it can be challenging to isolate signal from noise when low-biomass samples are being analyzed. We tested the hypothesis that stochastic sequencing noise, separable from reagent contamination, is generated during sequencing on the Illumina MiSeq platform when DNA input is below a critical threshold. We first purified DNA from serial dilutions of and from negative controls using three DNA purification kits, quantified input using droplet digital PCR, and then sequenced the 16S rRNA gene in four technical replicates.
View Article and Find Full Text PDFIdiopathic pulmonary fibrosis (IPF) causes considerable global morbidity and mortality, and its mechanisms of disease progression are poorly understood. Recent observational studies have reported associations between lung dysbiosis, mortality, and altered host defense gene expression, supporting a role for lung microbiota in IPF. However, the causal significance of altered lung microbiota in disease progression is undetermined.
View Article and Find Full Text PDFIntroduction: Despite strong evidence that maturation patterns of the gut microbiome in early life influence the risk for childhood asthma, very little is known about gut microbiota patterns in adults with established asthma, and of greater interest relationships to phenotypic features that characterise asthma heterogeneity.
Methods: Fifty-eight faecal samples from 32 adults with (n=24) and without (n=8) asthma were analysed using 16S ribosomal RNA gene sequencing methods to characterise intestinal bacterial composition. Compositional stability of paired samples was evaluated and features of gut bacterial community structure analysed in relation to extensive clinical characterisation data collected from subjects, who were enrolled in a prospective observational cohort study at the University of Michigan.
Int J Chron Obstruct Pulmon Dis
January 2019
Background: The role of airway microbiota in COPD is highly debated. Symptomology assessment is vital for the management of clinically stable COPD patients; however, the link between symp toms and the airway microbiome is currently unknown.
Purpose: The present study aimed to evaluate the relationship among stable COPD patients.
Am J Respir Crit Care Med
November 2018
Rationale: Hematopoietic cell transplant (HCT) is a common treatment for hematological neoplasms and autoimmune disorders. Among HCT recipients, pulmonary complications are common, morbid, and/or lethal, and they have recently been associated with gut dysbiosis. The role of lung microbiota in post-HCT pulmonary complications is unknown.
View Article and Find Full Text PDFRationale: The "gut-lung axis" is commonly invoked to explain the microbiome's influence on lung inflammation. Yet the lungs harbor their own microbiome, which is altered in respiratory disease. The relative influence of gut and lung bacteria on lung inflammation is unknown.
View Article and Find Full Text PDFWe report here the first complete genome sequence of a human isolate, strain AU1044, and the draft genomes of 11 other clinical strains, isolated from the lungs of cystic fibrosis patients. The genome of strain AU1044 is 4.81 Mb and encodes seven 16S rRNAs.
View Article and Find Full Text PDFRationale: Sepsis causes brain dysfunction and neuroinflammation. It is unknown whether neuroinflammation in sepsis is initiated by dissemination of bacteria to the brain and sustained by persistent infection, or whether neuroinflammation is a sterile process resulting solely from circulating inflammatory mediators.
Objectives: To determine if gut bacteria translocate to the brain during sepsis, and are associated with neuroinflammation.