C15-04 An Altered Respiratory Microbiome in Commonly Used Asthma Treatments

Abstract Rationale Next generation sequencing specifically 16S rRNA sequencing has facilitated more accurate microbial identification offering a more comprehensive understanding of the microbial communities that reside within the lung. Current studies report distinct microbial signatures that correlate with asthma pathophysiology, phenotype and with increasing evidence treatment response specific to inhaled corticosteroids. The study of individual microbial signatures may contribute to precision medicine approaches, identifying microbial signatures that may guide personalized therapy or serve as novel biomarkers of disease activity and progression. Methods This was a prospective observational study with a non-invasive (n = 58) and invasive arm (n = 27) recruiting patients with respiratory symptoms and a physician diagnosis of asthma. Participants were phenotyped based on clinical features, Th2 biomarkers and physiologic parameters and had biosamples (OR; oral rinse, NS; nasopharyngeal swab, SS; sputum sample, BAL; bronchoalveolar lavage) collected longitudinally. 16S rRNA sequencing was used to examine differences in microbial diversity, composition and taxonomic enrichment before and after (i) starting Nasal Corticosteroid (NCS) (ii) stopping Inhaled Corticosteroid (ICS) (iii) starting Biologic therapy. Results In those who started NCS (n = 35), sinonasal symptoms improved significantly (p = 0.01). Alpha diversity decreased while beta diversity and overall enrichment were unchanged in NS. Responders showed enrichment of Finegoldia and Anaerococcus; non-responders showed Leptotrichia . In those who stopped ICS (n = 16), asthma like symptoms improved (p = 0.01). There was no significant change in read counts, alpha or beta diversity in SS. Responders had higher Streptococcus, Lactobacillus, Prevotella, Actinomyces, while non-responders had distinct enrichment of Prevotella, Leptotrichia, Neisseria, Fusobacterium, Veillonella . In those who started a biologic (n = 6), all showed clinical response with FeNO reduction (p = 0.013) and improved FEV₁ (p = 0.041). Diversity metrics in paired OR and BAL were unchanged; taxa enriched post-biologic included Haemophilus, Streptococcus, Prevotella in OR and Prevotella, Veillonella, Porphyromonas in BAL. Conclusions In this study, we show that treatment strategies commonly used for asthma result in a significant change in the microbial micro-environment across the respiratory tract. Some of these may be associated with treatment response. Specifically, with biologic therapy, site-specific taxonomic signals identified warrant confirmation in larger studies in identifying patients more likely to respond to therapy. This abstract is funded by: Charitable Infirmary Charitable Trust