Unsung Heroes? De-Coding the Protective Effects of Airway Microbiota in COPD
Unsung Heroes? De-Coding the Protective Effects of Airway Microbiota in COPD
Accelerated Lung Function Decline and Mucus-Microbe Evolution in Chronic Obstructive Pulmonary Disease
Accelerated Lung Function Decline and Mucus-Microbe Evolution in Chronic Obstructive Pulmonary Disease
Progressive lung function loss is recognized in COPD; however, no study concurrently evaluates how accelerated lung function decline relates to mucus properties and the microbiome in COPD.
Airway 'Resistotypes' and Clinical Outcomes in Bronchiectasis
Airway 'Resistotypes' and Clinical Outcomes in Bronchiectasis
Application of whole-genome shotgun metagenomics to the airway microbiome in bronchiectasis highlights a diverse pool of antimicrobial resistance genes: the 'resistome', the clinical significance of which remains unclear.
Reply to Ward
Microbial Dysregulation of the Gut-Lung Axis in Bronchiectasis
Microbial Dysregulation of the Gut-Lung Axis in Bronchiectasis
Emerging data support the existence of a microbial "gut-lung" axis that remains unexplored in bronchiectasis. Prospective and concurrent sampling of gut (stool) and lung (sputum) was performed in a cohort of = 57 individuals with bronchiectasis and subjected to bacteriome (16S rRNA) and mycobiome (18S Internal Transcribed Spacer) sequencing (total, 228 microbiomes). Shotgun metagenomics was performed in a subset ( = 15; 30 microbiomes). Data from gut and lung compartments were integrated by weighted similarity network fusion, clustered, and subjected to co-occurrence analysis to evaluate gut-lung networks. Murine experiments were undertaken to validate specific driven gut-lung interactions. Microbial communities in stable bronchiectasis demonstrate a significant gut-lung interaction. Multibiome integration followed by unsupervised clustering reveals two patient clusters, differing by gut-lung interactions and with contrasting clinical phenotypes. A high gut-lung interaction cluster, characterized by lung , gut , and gut , is associated with increased exacerbations and greater radiological and overall bronchiectasis severity, whereas the low gut-lung interaction cluster demonstrates an overrepresentation of lung commensals, including , , and with gut . The lung gut relationship, observed in the high gut-lung interaction bronchiectasis cluster, was validated in a murine model of lung infection. This interaction was abrogated after antibiotic (imipenem) pretreatment in mice confirming the relevance and therapeutic potential of targeting the gut microbiome to influence the gut-lung axis. Metagenomics in a subset of individuals with bronchiectasis corroborated our findings from targeted analyses. A dysregulated gut-lung axis, driven by lung , associates with poorer clinical outcomes in bronchiectasis.
Neisseria species as pathobionts in bronchiectasis
Neisseria species as pathobionts in bronchiectasis
Neisseria species are frequently identified in the bronchiectasis microbiome, but they are regarded as respiratory commensals. Using a combination of human cohorts, next-generation sequencing, systems biology, and animal models, we show that bronchiectasis bacteriomes defined by the presence of Neisseria spp. associate with poor clinical outcomes, including exacerbations. Neisseria subflava cultivated from bronchiectasis patients promotes the loss of epithelial integrity and inflammation in primary epithelial cells. In vivo animal models of Neisseria subflava infection and metabolipidome analysis highlight immunoinflammatory functional gene clusters and provide evidence for pulmonary inflammation. The murine metabolipidomic data were validated with human Neisseria-dominant bronchiectasis samples and compared with disease in which Pseudomonas-, an established bronchiectasis pathogen, is dominant. Metagenomic surveillance of Neisseria across various respiratory disorders reveals broader importance, and the assessment of the home environment in bronchiectasis implies potential environmental sources of exposure. Thus, we identify Neisseria species as pathobionts in bronchiectasis, allowing for improved risk stratification in this high-risk group.
The current understanding and future directions for sputum microbiome profiling in chronic obstructive pulmonary disease
The current understanding and future directions for sputum microbiome profiling in chronic obstructive pulmonary disease
Next-generation sequencing (NGS) has deepened our understanding of the respiratory microbiome in health and disease. The number of microbiome studies employing sputum as an airway surrogate has continued to increase over the past decade to include multiple large multicentre and longitudinal studies of the microbiome in chronic obstructive pulmonary disease (COPD). In this review, we summarize the recent advances to our understanding of the bacteriome, virome and mycobiome in COPD.
Microbiology and the Microbiome in Bronchiectasis
Microbiology and the Microbiome in Bronchiectasis
The microbiology in bronchiectasis has been historically defined by culture-based analysis of the airway microbiome and to date has largely focused on the detection and eradication of specific bacterial pathogens. Although central to our current understanding of disease, microbial culture alone masks the holistic complexity of the microbiome and does not account for potential microbial interactions that define specific clinical phenotypes such as frequent exacerbators. Advances in next-generation sequencing including their analytical technologies can further complement and build upon our current understanding of the microbiology and microbiome in bronchiectasis providing improved patient stratification with prognostic significance.
The Airway Microbiome: Present and Future Applications
High Frequency of Allergic Bronchopulmonary Aspergillosis in Bronchiectasis-COPD Overlap
High Frequency of Allergic Bronchopulmonary Aspergillosis in Bronchiectasis-COPD Overlap
Allergic bronchopulmonary aspergillosis (ABPA) is associated with frequent exacerbations and poor outcomes in chronic respiratory disease, but remains underdiagnosed. The role of fungal sensitization in bronchiectasis-COPD overlap (BCO) is unknown.
Respiratory Mycoses in COPD and Bronchiectasis
Respiratory Mycoses in COPD and Bronchiectasis
Chronic obstructive pulmonary disease (COPD) and bronchiectasis represent chronic airway diseases associated with significant morbidity and mortality. Bacteria and viruses are commonly implicated in acute exacerbations; however the significance of fungi in these airways remains poorly defined. While COPD and bronchiectasis remain recognized risk factors for the occurrence of Aspergillus-associated disease including chronic and invasive aspergillosis, underlying mechanisms that lead to the progression from colonization to invasive disease remain uncertain. Nonetheless, advances in molecular technologies have improved our detection, identification and understanding of resident fungi characterizing these airways. Mycobiome sequencing has revealed the complex varied and myriad profile of airway fungi in COPD and bronchiectasis, including their association with disease presentation, progression, and mortality. In this review, we outline the emerging evidence for the clinical importance of fungi in COPD and bronchiectasis, available diagnostic modalities, mycobiome sequencing approaches and association with clinical outcomes.
Human and Porcine Transmission of Clostridioides difficile Ribotype 078, Europe
Human and Porcine Transmission of Clostridioides difficile Ribotype 078, Europe
Genomic analysis of a diverse collection of Clostridioides difficile ribotype 078 isolates from Ireland and 9 countries in Europe provided evidence for complex regional and international patterns of dissemination that are not restricted to humans. These isolates are associated with C. difficile colonization and clinical illness in humans and pigs.
Similarity network fusion for the integration of multi-omics and microbiomes in respiratory disease
Similarity network fusion for the integration of multi-omics and microbiomes in respiratory disease
Aspergillus-Associated Endophenotypes in Bronchiectasis
Aspergillus-Associated Endophenotypes in Bronchiectasis
Bronchiectasis is a chronic condition of global relevance resulting in permanent and irreversible structural airway damage. Bacterial infection in bronchiectasis is well studied; however, recent molecular studies identify fungi as important pathogens, either independently or in association with bacteria. species are established fungal pathogens in cystic fibrosis and their role is now increasingly being recognized in noncystic fibrosis bronchiectasis. While the healthy airway is constantly exposed to ubiquitously present conidia in the environment, anatomically damaged airways appear more prone to colonization and subsequent infection by this fungal group. possess diverse immunopathological mechanistic capabilities and when coupled with innate immune defects in a susceptible host, such as that observed in bronchiectasis, it may promote a range of clinical manifestations including sensitization, allergic bronchopulmonary aspergillosis, bronchitis, and/or invasive aspergillosis. How such clinical states influence "endophenotypes" in bronchiectasis is therefore of importance, as each associated disease state has overlapping features with bronchiectasis itself, and can evolve, depending on underlying host immunity from one type into another. Concurrent infection complicates the clinical course and exacerbations in bronchiectasis and therefore dedicated research to better understand the -host interaction in the bronchiectasis airway is now warranted.
On Bugs and Blowholes: Why Is Aspiration the Rule, Not the Exception?
On Bugs and Blowholes: Why Is Aspiration the Rule, Not the Exception?
Integrative microbiomics in bronchiectasis exacerbations
Integrative microbiomics in bronchiectasis exacerbations
Bronchiectasis, a progressive chronic airway disease, is characterized by microbial colonization and infection. We present an approach to the multi-biome that integrates bacterial, viral and fungal communities in bronchiectasis through weighted similarity network fusion ( https://integrative-microbiomics.ntu.edu.sg ). Patients at greatest risk of exacerbation have less complex microbial co-occurrence networks, reduced diversity and a higher degree of antagonistic interactions in their airway microbiome. Furthermore, longitudinal interactome dynamics reveals microbial antagonism during exacerbation, which resolves following treatment in an otherwise stable multi-biome. Assessment of the Pseudomonas interactome shows that interaction networks, rather than abundance alone, are associated with exacerbation risk, and that incorporation of microbial interaction data improves clinical prediction models. Shotgun metagenomic sequencing of an independent cohort validated the multi-biome interactions detected in targeted analysis and confirmed the association with exacerbation. Integrative microbiomics captures microbial interactions to determine exacerbation risk, which cannot be appreciated by the study of a single microbial group. Antibiotic strategies probably target the interaction networks rather than individual microbes, providing a fresh approach to the understanding of respiratory infection.
A high-risk airway mycobiome is associated with frequent exacerbation and mortality in COPD
A high-risk airway mycobiome is associated with frequent exacerbation and mortality in COPD
The chronic obstructive pulmonary disease (COPD) bacteriome associates with disease severity, exacerbations and mortality. While COPD patients are susceptible to fungal sensitisation, the role of the fungal mycobiome remains uncertain.
Erratum for Vidaillac et al. "Sex Steroids Induce Membrane Stress Responses and Virulence Properties in Pseudomonas aeruginosa"
Erratum for Vidaillac et al. "Sex Steroids Induce Membrane Stress Responses and Virulence Properties in Pseudomonas aeruginosa"
Sex Steroids Induce Membrane Stress Responses and Virulence Properties in Pseudomonas aeruginosa
Sex Steroids Induce Membrane Stress Responses and Virulence Properties in Pseudomonas aeruginosa
Estrogen, a major female sex steroid hormone, has been shown to promote the selection of mucoid in the airways of patients with chronic respiratory diseases, including cystic fibrosis. This results in long-term persistence, poorer clinical outcomes, and limited therapeutic options. In this study, we demonstrate that at physiological concentrations, sex steroids, including testosterone and estriol, induce membrane stress responses in This is characterized by increased virulence and consequent inflammation and release of proinflammatory outer membrane vesicles promoting persistence of the bacteria. The steroid-induced response correlates with the molecular polarity of the hormones and membrane fluidic properties of the bacteria. This novel mechanism of interaction between sex steroids and explicates the reported increased disease severity observed in females with cystic fibrosis and provides evidence for the therapeutic potential of the modulation of sex steroids to achieve better clinical outcomes in patients with hormone-responsive strains. Molecular mechanisms by which sex steroids interact with to modulate its virulence have yet to be reported. Our work provides the first characterization of a steroid-induced membrane stress mechanism promoting virulence, which includes the release of proinflammatory outer membrane vesicles, resulting in inflammation, host tissue damage, and reduced bacterial clearance. We further demonstrate that at nanomolar (physiological) concentrations, male and female sex steroids promote virulence in clinical strains of based on their dynamic membrane fluidic properties. This work provides, for the first-time, mechanistic insight to better understand and predict the related response to sex steroids and explain the interindividual patient variability observed in respiratory diseases such as cystic fibrosis that are complicated by gender differences and chronic infection.
Mathematical-based microbiome analytics for clinical translation
Mathematical-based microbiome analytics for clinical translation
Traditionally, human microbiology has been strongly built on the laboratory focused culture of microbes isolated from human specimens in patients with acute or chronic infection. These approaches primarily view human disease through the lens of a single species and its relevant clinical setting however such approaches fail to account for the surrounding environment and wide microbial diversity that exists Given the emergence of next generation sequencing technologies and advancing bioinformatic pipelines, researchers now have unprecedented capabilities to characterise the human microbiome in terms of its taxonomy, function, antibiotic resistance and even bacteriophages. Despite this, an analysis of microbial communities has largely been restricted to ordination, ecological measures, and discriminant taxa analysis. This is predominantly due to a lack of suitable computational tools to facilitate microbiome analytics. In this review, we first evaluate the key concerns related to the inherent structure of microbiome datasets which include its compositionality and batch effects. We describe the available and emerging analytical techniques including integrative analysis, machine learning, microbial association networks, topological data analysis (TDA) and mathematical modelling. We also present how these methods may translate to clinical settings including tools for implementation. Mathematical based analytics for microbiome analysis represents a promising avenue for clinical translation across a range of acute and chronic disease states.