Species-level, metagenomic and proteomic analysis of microbe-immune interactions in severe asthma

Journal article

Background: The airway microbiome in severe asthma has not been characterised at species-level by metagenomic sequencing, nor have the relationships between specific species and mucosal immune responses in ‘type-2 low’, neutrophilic asthma been defined. We performed an integrated species-level metagenomic data with inflammatory mediators to characterise prevalence of dominant potentially pathogenic organisms and host immune responses.

Methods: Sputum and nasal lavage samples were analysed using long-read metagenomic sequencing with Nanopore and qPCR in two cross-sectional adult severe asthma cohorts, Wessex (n=66) and Oxford (n=30). We integrated species-level data with clinical parameters and 39 selected airway proteins measured by immunoassay and O-link.

Results: The sputum microbiome in health and mild asthma displayed comparable microbial diversity. By contrast, 23% (19/81) of severe asthma microbiomes were dominated by a single respiratory pathogen, namely H. influenzae (n=10), M. catarrhalis (n=4), S. pneumoniae (n=4) and P. aeruginosa (n=1). Neutrophilic asthma was associated with H. influenzae, M. catarrhalis, S. pneumoniae and T. whipplei with elevated type-1 cytokines and proteases; eosinophilic asthma with higher M. catarrhalis, but lower H. influenzae, and S. pneumoniae abundance. H. influenzae load correlated with Eosinophil Cationic Protein, elastase and IL-10. R. mucilaginosa associated positively with IL-6 and negatively with FGF. Bayesian network analysis also revealed close and distinct relationships of H. influenzae and M. catarrhalis with type-1 airway inflammation. The microbiomes and cytokine milieu were distinct between upper and lower airways.

Conclusions: This species-level integrated analysis reveals central, but distinct associations between potentially pathogenic bacteria and airways inflammation in severe asthma.

Authors: Jabeen, M; Sanderson, N; Tine, M; Donachie, G; Barber, C

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Allergy
• Volume: 79
• Issue: 11
• Pages: 2966-2980
• Publication date: 2024-08-11
• Acceptance date: 2024-06-19
• DOI: 10.1111/all.16269
• EISSN: 1398-9995
• ISSN: 0105-4538
• Language: English
• Keywords: sputum; asthma; microbiome; cytokine; bacteria