Publications

Emerging evidence demonstrates the evolving role of fungi in the pathophysiology and disease progression observed in bronchiectasis. Fungal-associated traits are linked to disease severity, exacerbation frequency and airway inflammation. Structural abnormalities and impaired mucociliary clearance, characteristic of bronchiectasis, predispose to fungal colonisation, with subsequent immunopathogenic responses dependent on underlying host immunity. The diagnosis of fungal infection remains challenging in clinical settings, owing to the limitations of existing diagnostic modalities; however, the development of culture-independent molecular techniques shows promise. The use of next-generation sequencing has significantly advanced our understanding of the fungal microbiome in bronchiectasis, identifying fungi that are challenging to culture. Integrative microbiomics further elucidates the intricate and dynamic role of fungi in relation to other microbial kingdoms, and across distant organs such as the gut, revealing important relationships with bacterial pathogens including Pseudomonas aeruginosa. Airway inflammatory profiling has shown fungal-associated inflammatory endotypes which may serve as treatable traits. Environmental influences on fungi and bronchiectasis-exacerbated by air pollution and climate change-underscore the key role of the exposome in fungal-associated endotypes in bronchiectasis. This review outlines the clinical significance of fungi in bronchiectasis, the current diagnostic and treatment challenges, and emerging fungal-associated endotypes in the context of environmental influence on disease.

The contribution of airway pathobionts to chronic respiratory disease is increasingly recognized, yet the evolutionary processes that shift commensals to pathogens remain poorly understood. Here we investigate how antibiotic pressure drives adaptation in Neisseria subflava, a common airway commensal associated with bronchiectasis. Using serial passage under ceftriaxone exposure, we observe a >300-fold increase in resistance, accompanied by enhanced biofilm formation and genetic reprogramming. Whole-genome sequencing reveals recurrent mutations in the adhesin gene ataA, while single-cell transcriptomics identifies six functionally distinct clusters indicating adaptive programs in growth, metal homeostasis, oxidative stress, and cell-wall remodeling. Notably, biofilm integrity is maintained through compensatory upregulation of comP and bamE, which promotes phagocytic evasion and resistance in experimentally evolved strains and clinical isolates. Iron availability further stabilizes biofilm and modulates antibiotic tolerance, underscoring metal homeostasis as a contributory adaptive axis. Together, these findings reveal a multifaceted strategy by which N. subflava exploits antibiotic selection to transition towards pathogenicity. By integrating experimental evolution with single-cell resolution, we establish a framework for understanding the commensal-to-pathobiont transition, with broad implications for the airway microbiome and antimicrobial resistance in chronic respiratory disease.

The global burden of bacterial respiratory infections, now among the leading causes of mortality worldwide, has been exacerbated by the rise of antimicrobial resistance. This has highlighted significant gaps in current management strategies, underscoring the need for deeper insights into bacterial pathogenesis.

The discoveries of neutrophilic inflammation and Pseudomonas-dominant pulmonary dysbiosis have helped pave the way for host-directed therapy in bronchiectasis. Substantial knowledge gaps still remain about the interplay between neutrophilic signatures and microbes in non-tuberculous mycobacterial lung disease (NTM-LD), a phenotypically diverse lung infection that is increasingly prevalent in the United States and other parts of the world.

Interest in bronchiectasis is increasing and no prior study has used artificial intelligence (AI) to interrogate its rich, multidimensional literature to characterise research trends, themes and knowledge gaps.

The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) registry shows considerable variation in culturable microbes in sputum between different European countries. The additive role of next-generation metagenomic sequencing remains unexplored and the association with antimicrobial resistomes unknown.

Workplace exposure to printer toner-emitted nanoparticles at commercial printing facilities poses respiratory health risks to workers on the printing floor, however, its impact on environmental and airway microbiomes and how this relates to worker health remains unknown. To investigate this, we prospectively evaluated five printing centres in Singapore, collecting air samples from office areas and printing floors and airway specimens from workers stationed in office or printing floor areas. All specimens were subjected to targeted amplicon sequencing to determine bacteriome and mycobiome profiles. Relationships between nanoparticle exposure levels, air and airway microbiomes were assessed. We reveal that nanoparticle exposure at printing facilities was significantly associated with shifts in air microbiome profiles in high-exposure printing areas relative to low-exposure office areas. Microbiome correlates of indoor air chemical exposures, mainly polycyclic aromatic hydrocarbons (PAHs) and trace elements, were identified. Lung function and airway microbiomes were influenced by nanoparticle exposure where printing floor workers demonstrate reduced lung function, independent of exposure level, with airway microbiomes characterized by enrichment of Chryseobacterium, Porphyromonas and Candida. Assessment of potential air-airway microbial crossover at each site, accounting for nanoparticle exposure levels, reveals significant increases in bacterial but not fungal crossover in printing floor workers. Taken together, this study demonstrates altered environmental and airway microbiomes at commercial printing facilities and in printing floor workers. Further research is needed to assess the long-term health impacts of such exposure including the potential for microbial profiling in printing facility design and operation.

Advances in DNA sequencing and analysis of the respiratory microbiome highlight its close association with bronchiectasis phenotypes, revealing fresh opportunities for diagnosis, stratification, and personalized clinical intervention. An under-recognized condition, bronchiectasis is increasingly the subject of recent large-scale, multicentre, and longitudinal clinical studies including detailed analysis of the microbiome. In this review, we summarize recent progress in our understanding of the bronchiectasis microbiome within the context of its potential use in treatment decisions.

Sensitisation to is linked to worse outcomes in patients with COPD; however, its prevalence and clinical implications in domestic (residential) settings remains unknown.

Progressive lung function loss is recognized in chronic obstructive pulmonary disease (COPD); however, no study concurrently evaluates how accelerated lung function decline relates to mucus properties and the microbiome in COPD. Longitudinal assessment of mucus and microbiome changes accompanying accelerated lung function decline in patients COPD. This was a prospective, longitudinal assessment of the London COPD cohort exhibiting the greatest FEV decline ( = 30; accelerated decline; 156 ml/yr FEV loss) and with no FEV decline ( = 28; nondecline; 49 ml/yr FEV gain) over time. Lung microbiomes from paired sputum (total 116 specimens) were assessed by shotgun metagenomics and corresponding mucus profiles evaluated for biochemical and biophysical properties. Biochemical and biophysical mucus properties are significantly altered in the accelerated decline group. Unsupervised principal component analysis showed clear separation, with mucus biochemistry associated with accelerated decline, whereas biophysical mucus characteristics contributed to interindividual variability. When mucus and microbes are considered together, an accelerated decline mucus-microbiome association emerges, characterized by increased mucin (MUC5AC [mucin 5AC] and MUC5B [mucin 5B]) concentration and the presence of and . As COPD progresses, mucus-microbiome shifts occur, initially characterized by low mucin concentration and transition from viscous to elastic dominance accompanied by the commensals , , , and (Global Initiative for Chronic Obstructive Lung Disease [GOLD] A and B) before transition to increased mucus viscosity, mucins, and DNA concentration together with the emergence of pathogenic microorganisms including , , and (GOLD E). Mucus-microbiome associations evolve over time with accelerated lung function decline, symptom progression, and exacerbations affording fresh therapeutic opportunities for early intervention.

Chronic infection and inflammation shapes the airway microbiome in bronchiectasis. Utilizing whole-genome shotgun metagenomics to analyze the airway resistome provides insight into interplay between microbes, resistance genes, and clinical outcomes. To apply whole-genome shotgun metagenomics to the airway microbiome in bronchiectasis to highlight a diverse pool of antimicrobial resistance genes: the "resistome," the clinical significance of which remains unclear. Individuals with bronchiectasis were prospectively recruited into cross-sectional and longitudinal cohorts ( = 280), including the international multicenter cross-sectional Cohort of Asian and Matched European Bronchiectasis 2 (CAMEB 2) study ( = 251) and two independent cohorts, one describing patients experiencing acute exacerbation and a further cohort of patients undergoing eradication treatment. Sputum was subjected to metagenomic sequencing, and the bronchiectasis resistome was evaluated in association with clinical outcomes and underlying host microbiomes. The bronchiectasis resistome features a unique resistance gene profile and increased counts of aminoglycoside, bicyclomycin, phenicol, triclosan, and multidrug resistance genes. Longitudinally, it exhibits within-patient stability over time and during exacerbations despite between-patient heterogeneity. Proportional differences in baseline resistome profiles, including increased macrolide and multidrug resistance genes, associate with shorter intervals to the next exacerbation, whereas distinct resistome archetypes associate with frequent exacerbations, poorer lung function, geographic origin, and the host microbiome. Unsupervised analysis of resistome profiles identified two clinically relevant "resistotypes," RT1 and RT2, the latter characterized by poor clinical outcomes, increased multidrug resistance, and Successful targeted eradication in -colonized individuals mediated reversion from RT2 to RT1, a more clinically favorable resistome profile demonstrating reduced resistance gene diversity. The bronchiectasis resistome associates with clinical outcomes, geographic origin, and the underlying host microbiome. Bronchiectasis resistotypes link to clinical disease and are modifiable through targeted antimicrobial therapy.

Studies on the impact of intermittent fasting on periodontal health are still scarce. Thus, this study evaluated the effects of long-term intermittent fasting on periodontal health and the subgingival microbiota.

Bronchiectasis is marked by bronchial dilatation, recurrent infections and significant morbidity, underpinned by a complex interplay between microbial dysbiosis and immune dysregulation. The identification of distinct endophenotypes have refined our understanding of its pathogenesis, including its heterogeneous disease mechanisms that influence treatment and prognosis responses. Next-generation sequencing (NGS) has revolutionised the way we view airway microbiology, allowing insights into the "unculturable". Understanding the bronchiectasis microbiome through targeted amplicon sequencing and/or shotgun metagenomics has provided key information on the interplay of the microbiome and host immunity, a central feature of disease progression. The rapid increase in translational and clinical studies in bronchiectasis now provides scope for the application of precision medicine and a better understanding of the efficacy of interventions aimed at restoring microbial balance and/or modulating immune responses. Holistic integration of these insights is driving an evolving paradigm shift in our understanding of bronchiectasis, which includes the critical role of the microbiome and its unique interplay with clinical, inflammatory, immunological and metabolic factors. Here, we review the current state of infection and the microbiome in bronchiectasis and provide views on the future directions in this field.

Bronchiectasis presents a significant challenge due to its rising prevalence, associated economic burden and clinical heterogeneity. This review synthesises contemporary understanding and literature of bronchiectasis exacerbations, addressing the transition from stable state to exacerbations, underlining the importance of early and precise recognition, rigorous severity assessment, prompt treatment, and prevention measures, as well as emphasising the need for strategies to assess and improve early and long-term patient outcomes. The review highlights the interplay between stable state phases and exacerbations in bronchiectasis, introducing the concept of "exogenous and endogenous changes in airways homeostasis" and the "adapted island model" with a particular focus on "frequent exacerbators", a group of patients associated with specific clinical characteristics and worse outcomes. The pathophysiology of exacerbations is explored through the lens of microbial and nonmicrobial triggers and the presence and the activity of comorbidities, elaborating on the impact of both exogenous insults, such as infections and pollution, and endogenous factors such as inflammatory endotypes. Finally, the review proposes a multidisciplinary approach to care, integrating advancements in precision medicine and biomarker research, paving the way for tailored treatments that challenge the traditional antibiotic paradigm.

This review summarizes our current understanding of the respiratory microbiome in COPD and Bronchiectasis. We explore the interplay between microbial communities, host immune responses, disease pathology, and treatment outcomes.