Bridging the airway microbiome and targeted therapy in bronchiectasis: multi-omics insights, endotypes and emerging therapies
8 affiliations
- 1Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, Canada
- 2Department of Medicine, University of Calgary, Calgary, AB Canada
- 3C.S. Thornton and M.A. Mall contributed equally to this article as lead authors
- 4Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- 5German Center for Lung Research (DZL), associated partner site Berlin, Berlin, Germany
- 6German Center for Child and Adolescent Health (DZKJ), partner site Berlin, Berlin, Germany
- 7School of Pharmacy, Queen's University Belfast, Belfast, UK
- 8Cluster of Excellence ImmunoPreCept, Charité – Universitätsmedizin Berlin, Berlin, Germany
Abstract
Bronchiectasis is a heterogeneous chronic airway disease primarily driven by persistent infection, microbial dysbiosis and dysregulated host immunity. While culture-based microbiology has historically informed clinical management, advances in high-throughput sequencing and multi-omic technologies have transformed our understanding of the airway ecosystem, revealing that disease activity is shaped not only by individual pathogens, but by complex and dynamic host–microbe interactions. Despite the breadth of descriptive microbiome data, translation into clinically actionable diagnostics or therapies has been limited. Importantly, cross-sectional correlations between microbiota and inflammation do not establish cause and effect, underscoring the need to embed host–microbiome profiling within both longitudinal and interventional therapeutic trials. In this review, we critically appraise current microbial and host multi-omics research in bronchiectasis, integrating microbiome studies with host inflammatory, proteomic and immunophenotyping data. We highlight themes emerging across cohorts, including low microbial diversity, pathogen dominance, loss of commensal networks and neutrophil-driven inflammation, and discuss how these features align with biological endotypes associated with exacerbations and treatment response. Drawing on lessons from host-directed therapeutic successes, we examine translational roadblocks limiting microbiome-guided care. We further review emerging microbiome-modulating strategies such as pathogen-specific biologics, bacteriophage therapy, live biotherapeutic products, biofilm-targeting adjuncts and precision antibiotic stewardship. Finally, we propose a roadmap toward microbiome-informed precision medicine through harmonised methodologies, integration of host and microbial biomarkers into clinical trials, and embedding multi-omics pipelines within large international registries. Collectively, these advances have the potential to shift bronchiectasis research and clinical management towards rationally designed, precision medicine-driven therapeutic strategies.
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BibTeX
@article{thornton2026bridging,
title = {{Bridging the airway microbiome and targeted therapy in bronchiectasis: multi-omics insights, endotypes and emerging therapies}},
author = {Christina S. Thornton and Laura Schaupp and Michael M. Tunney and Marcus A. Mall},
journal = {The European Respiratory Journal},
year = {2026},
month = sep,
doi = {10.1183/13993003.00239-2026},
url = {https://doi.org/10.1183/13993003.00239-2026},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Bridging the airway microbiome and targeted therapy in bronchiectasis: multi-omics insights, endotypes and emerging therapies
AU - Christina S. Thornton
AU - Laura Schaupp
AU - Michael M. Tunney
AU - Marcus A. Mall
PY - 2026
DA - 2026/09/08
JO - The European Respiratory Journal
DO - 10.1183/13993003.00239-2026
UR - https://doi.org/10.1183/13993003.00239-2026
AB - Bronchiectasis is a heterogeneous chronic airway disease primarily driven by persistent infection, microbial dysbiosis and dysregulated host immunity. While culture-based microbiology has historically informed clinical management, advances in high-throughput sequencing and multi-omic technologies have transformed our understanding of the airway ecosystem, revealing that disease activity is shaped not only by individual pathogens, but by complex and dynamic host–microbe interactions. Despite the breadth of descriptive microbiome data, translation into clinically actionable diagnostics or therapies has been limited. Importantly, cross-sectional correlations between microbiota and inflammation do not establish cause and effect, underscoring the need to embed host–microbiome profiling within both longitudinal and interventional therapeutic trials. In this review, we critically appraise current microbial and host multi-omics research in bronchiectasis, integrating microbiome studies with host inflammatory, proteomic and immunophenotyping data. We highlight themes emerging across cohorts, including low microbial diversity, pathogen dominance, loss of commensal networks and neutrophil-driven inflammation, and discuss how these features align with biological endotypes associated with exacerbations and treatment response. Drawing on lessons from host-directed therapeutic successes, we examine translational roadblocks limiting microbiome-guided care. We further review emerging microbiome-modulating strategies such as pathogen-specific biologics, bacteriophage therapy, live biotherapeutic products, biofilm-targeting adjuncts and precision antibiotic stewardship. Finally, we propose a roadmap toward microbiome-informed precision medicine through harmonised methodologies, integration of host and microbial biomarkers into clinical trials, and embedding multi-omics pipelines within large international registries. Collectively, these advances have the potential to shift bronchiectasis research and clinical management towards rationally designed, precision medicine-driven therapeutic strategies.
SN - 0903-1936
SN - 1399-3003
ER -