In The Journal of allergy and clinical immunology
BACKGROUND : The response to inhaled corticosteroids (ICS) in asthma is affected by the interplay of several factors. Among these, the role of the upper-airway microbiome has been scarcely investigated. We aimed to evaluate the association between the salivary, pharyngeal, and nasal microbiome with asthma exacerbations despite ICS use.
METHODS : Samples from 250 asthma patients from the Genomics and Metagenomics of Asthma Severity (GEMAS) study treated with ICS were analyzed. Controls/cases were defined by the absence/presence of asthma exacerbations in the past six months despite being treated with ICS. The bacterial microbiota was profiled by sequencing the V3-V4 region of the 16S rRNA gene. Differences between groups were assessed by PERMANOVA and regression models adjusted for potential confounders. A false discovery rate (FDR) of 5% was used to correct for multiple comparisons. Classification models of asthma exacerbations despite ICS treatment were built with machine learning approaches based on clinical, genetic, and microbiome data.
RESULTS : In nasal and saliva samples, cases had lower bacterial diversity (Richness, Shannon, and Faith indexes) than controls (0.007≤p≤0.037). Asthma exacerbations accounted for 8-9% of the interindividual variation of the salivary and nasal microbiomes (0.003≤p≤0.046). Three, four, and eleven bacterial genera from the salivary, pharyngeal, and nasal microbiomes were differentially abundant between groups (4.09x10-12≤FDR≤0.047). Integrating clinical, genetic, and microbiome data showed good discrimination for the development of asthma exacerbations despite ICS use (AUCtraining:0.82 and AUCvalidation:0.77).
CONCLUSION : The diversity and composition of the upper-airway microbiome are associated with asthma exacerbations despite ICS treatment. The salivary microbiome has a potential application as a biomarker of asthma exacerbations despite ICS use.
Perez-Garcia Javier, González-Carracedo Mario, Espuela-Ortiz Antonio, Hernández-Pérez José M, González-Pérez Ruperto, Sardón-Prado Olaia, Martin-Gonzalez Elena, Mederos-Luis Elena, Poza-Guedes Paloma, Corcuera-Elosegui Paula, Callero Ariel, Sánchez-Machín Inmaculada, Korta-Murua Javier, Pérez-Pérez José A, Villar Jesús, Pino-Yanes Maria, Lorenzo-Diaz Fabian
2022-Nov-04
16S rRNA, asthma, biomarker, exacerbations, inhaled corticosteroids, microbiota, nasal, pharyngeal, precision medicine, saliva
