Abstract
<b>Background:</b> Microbiota dysbiosis is associated with progression of idiopathic pulmonary fibrosis (IPF). A retrospective study suggests lower hospitalization rate in IPF patients treated with azithromycin (AZT), an antibiotic (AB) known to affect microbiota in other respiratory diseases. <b>Aims and objectives:</b> To investigate the magnitude and duration of the effects of AZT on the upper and lower airway (AW) microbiota of IPF patients, as well as on its genetic potential to induce resistance to AZT. <b>Methods:</b> In a double-blind randomized controlled cross-over trial, 24 IPF patients underwent two 12-week interventions (AZT 500mg or placebo 3 times per week), separated by a 4-week wash-out (NCT02173145). Paired sputum and oropharyngeal swab samples were analysed by 16S rRNA gene sequencing. Bacterial burden and carriage of AB resistance genes were determined by real-time quantitative PCR. <b>Results:</b> AZT reduced microbiota richness and phylogenetic diversity in lower and upper AW but with a stronger and more persistent effect, still present 5 months after treatment, in lower AW. 4 out of 5 patients with increased carriage of AB resistance genes had a decrease in bacterial load and enrichment of the genus <i>Streptococcus</i> in lower AW. In contrast, 5 patients without increase in resistance genes had no change in bacterial load and enrichment of <i>Prevotella</i>. Microbiota dysbiosis was not correlated with changes in lung function over the study period. <b>Conclusions:</b> AZT leads to sustained changes of lower and upper AW microbiota in IPF patients. While these changes are not correlated to short-term changes in lung function or clinical status, longer-term follow-up studies are required.
Published Version
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