Abstract
Rationale: The airway microbiota is altered in asthma, with less Bacteriodetes and more Proteobacteria than in healthy individuals. AHR to mannitol is related to eosinophilic airway inflammation and mast cell activation, but the relationship between AHR to mannitol and changes in airway microbiota is currently unknown.
Aim: To examine the relative contribution of microbiota, eosinophilic inflammation and mast cell changes to AHR to mannitol in subjects with asthma.
Methods: In 20 steroid-free, non-smoking subjects with asthma, AHR to mannitol was examined and bacterial DNA was extracted from broncheo-alveolar lavage (BAL) and subjected to Illumina MiSeq sequencing of the 16S rDNA V4 region. Eosinophils and mast cells (tryptase+/chymase- and trytase+/chymase+) were quantified by immunohistochemistry and computerized image analysis.
Results: The relative abundance of Bacteroidetes was lower in asthmatics with AHR to mannitol compared to those without (median [IQR]: 18.4% [7.4] vs. 30.3% [16.8], p=0.006), whereas the relative abundance of Proteobacteria was higher (32.7% [11.4] vs. 24.8% [11.4], p=0.018). The degree of AHR to mannitol negatively correlated with the proportion of Bacteroidetes, rho(s): -0.61, p=0.002 and positively correlated with the proportion of Proteobacteria, rho(s): 0.54, p=0.008. The level of Bacteroidetes alone could explain 57% of the variation in AHR to mannitol independently of eosinophilic inflammation or mast cell phenotype.
Conclusion: AHR to mannitol is associated with changes in the airway microbiota, independently of eosinophilic inflammation and mast cell phenotype, suggesting that the airway microbiota may constitute a driver of AHR in asthma.
- Copyright ©ERS 2015