Abstract
BackgroundThis study of the oropharyngeal microbiome complements the previously published AZIthromycin in Severe ASThma (AZISAST) clinical trial, where the use of azithromycin was assessed in subjects with exacerbation-prone severe asthma. Here, we determined the composition of the oropharyngeal microbial community by means of deep sequencing of the amplified 16S rRNA gene in oropharyngeal swabs from patients with exacerbation-prone severe asthma, at baseline and during and after 6 months treatment with azithromycin or placebo.ResultsA total of 1429 OTUs were observed, of which only 59 were represented by more than 0.02% of the reads. Firmicutes, Bacteroidetes, Fusobacteria, Proteobacteria and Actinobacteria were the most abundant phyla and Streptococcus and Prevotella were the most abundant genera in all the samples. Thirteen species only accounted for two thirds of the reads and two species only, i.e. Prevotella melaninogenica and Streptococcus mitis/pneumoniae, accounted for one fourth of the reads.We found that the overall composition of the oropharyngeal microbiome in patients with severe asthma is comparable to that of the healthy population, confirming the results of previous studies. Long term treatment (6 months) with azithromycin increased the species Streptococcus salivarius approximately 5-fold and decreased the species Leptotrichia wadei approximately 5-fold. This was confirmed by Boruta feature selection, which also indicated a significant decrease of L. buccalis/L. hofstadtii and of Fusobacterium nucleatum. Four of the 8 treated patients regained their initial microbial composition within one month after cessation of treatment.ConclusionsDespite large diversity of the oropharyngeal microbiome, only a few species predominate. We confirm the absence of significant differences between the oropharyngeal microbiomes of people with and without severe asthma. Possibly, long term azithromycin treatment may have long term effects on the composition of the oropharygeal microbiome in half of the patients.
Highlights
This study of the oropharyngeal microbiome complements the previously published AZIthromycin in Severe ASThma (AZISAST) clinical trial, where the use of azithromycin was assessed in subjects with exacerbationprone severe asthma
The genetic and environmental factors that determine asthma are not well understood, but several studies suggest that microbes from oral sites contribute to colonization of the airways in disease [2,3,4], and that microbial colonization of the airways might have a role in the chronic inflammatory process [1, 5]
Patients with severe asthma and eosinophilic inflammation did not benefit from AZ treatment compared with placebo [12]
Summary
This study of the oropharyngeal microbiome complements the previously published AZIthromycin in Severe ASThma (AZISAST) clinical trial, where the use of azithromycin was assessed in subjects with exacerbationprone severe asthma. The genetic and environmental factors that determine asthma are not well understood, but several studies suggest that microbes from oral sites contribute to colonization of the airways in disease (as in cystic fibrosis) [2,3,4], and that microbial colonization of the airways might have a role in the chronic inflammatory process [1, 5] Both Chlamydophila pneumoniae and Mycoplasma pneumoniae have been detected in respiratory secretions from patients with acute asthma exacerbations [6,7,8]. The induction of antimicrobial resistance has been investigated in healthy individuals after short-term administration of macrolides, the effects of chronic treatment with macrolides on the composition of the pharyngeal microbiome in patients with (severe) asthma remain to be elucidated
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