AI Article Synopsis

  • Severe asthma (SA) has various clinical phenotypes linked to a diverse airway microbiome, and a study focused on identifying phenotypes with low microbial diversity.
  • Metagenomic sequencing of sputum samples from SA participants identified 51 out of 97 samples with relative dominant species (RDS), with Haemophilus influenzae being the most prevalent.
  • The research found that a specific cluster of RDSs associated with Haemophilus influenzae had more severe disease characteristics and indicated a host response linked to neutrophilic inflammation, suggesting potential for antibiotic treatment in this group.

Article Abstract

Background: Severe asthma (SA) encompasses several clinical phenotypes with a heterogeneous airway microbiome. We determined the phenotypes associated with a low α-diversity microbiome.

Methods: Metagenomic sequencing was performed on sputum samples from SA participants. A threshold of 2 standard deviations below the mean of α-diversity of mild-moderate asthma and healthy control subjects was used to define those with an abnormal abundance threshold as relative dominant species (RDS).

Findings: Fifty-one out of 97 SA samples were classified as RDSs with Haemophilus influenzae RDS being most common (n = 16), followed by Actinobacillus unclassified (n = 10), Veillonella unclassified (n = 9), Haemophilus aegyptius (n = 9), Streptococcus pseudopneumoniae (n = 7), Propionibacterium acnes (n = 5), Moraxella catarrhalis (n = 5) and Tropheryma whipplei (n = 5). Haemophilus influenzae RDS had the highest duration of disease, more exacerbations in previous year and greatest number on daily oral corticosteroids. Hierarchical clustering of RDSs revealed a C2 cluster (n = 9) of highest relative abundance of exclusively Haemophilus influenzae RDSs with longer duration of disease and higher sputum neutrophil counts associated with enrichment pathways of MAPK, NF-κB, TNF, mTOR and necroptosis, compared to the only other cluster, C1, which consisted of 7 Haemophilus influenzae RDSs out of 42. Sputum transcriptomics of C2 cluster compared to C1 RDSs revealed higher expression of neutrophil extracellular trap pathway (NETosis), IL6-transignalling signature and neutrophil activation.

Conclusion: We describe a Haemophilus influenzae cluster of the highest relative abundance associated with neutrophilic inflammation and NETosis indicating a host response to the bacteria. This phenotype of severe asthma may respond to specific antibiotics.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11347389PMC
http://dx.doi.org/10.1002/ctm2.70007DOI Listing

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