The upper-airway microbiome as a biomarker of asthma exacerbations despite inhaled corticosteroid treatment - 03/03/23
, Fabian Lorenzo-Diaz, PhD a, c, ⁎ Graphical abstract |
Abstract |
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 receipt of ICS.
Methods |
Samples from 250 asthma patients from the Genomics and Metagenomics of Asthma Severity (GEMAS) study treated with ICS were analyzed. Control/case subjects were defined by the absence/presence of asthma exacerbations in the past 6 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, case subjects had lower bacterial diversity (Richness, Shannon, and Faith indices) than control subjects (.007 ≤ P ≤ .037). Asthma exacerbations accounted for 8% to 9% of the interindividual variation of the salivary and nasal microbiomes (.003 ≤ P ≤ .046). Three, 4, and 11 bacterial genera from the salivary, pharyngeal, and nasal microbiomes were differentially abundant between groups (4.09 × 10−12 ≤ FDR ≤ 0.047). Integrating clinical, genetic, and microbiome data showed good discrimination for the development of asthma exacerbations despite receipt of ICS (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 receipt of ICS.
Le texte complet de cet article est disponible en PDF.Key words : 16S rRNA, asthma, biomarker, exacerbations, inhaled corticosteroids, microbiota, nasal, pharyngeal, precision medicine, saliva
Abbreviations used : AUC, FDR, GEMAS, ICS
Plan
| The last 2 authors contributed equally to this article, and both should be considered senior author. |
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| This study was funded by the Spanish Ministry of Science and Innovation, grant SAF2017-83417R awarded by MCIN/AEI/10.13039/501100011033, and European Regional Developmental Fund (ERDF) “A way of making Europe,” to M.P.-Y. and F.L.-D. M.P.-Y. and J.V. were also supported by CIBER–Consorcio Centro de Investigación Biomédica en Red (CIBERES), Instituto de Salud Carlos III (ISCIII), and the European Regional Development Fund (CB06/06/1088). This project was also partially funded by grant support from GlaxoSmithKline (Spain) through an agreement with Fundación Canaria Instituto de Investigación Sanitaria de Canarias (FIISC) to M.P.-Y. and J.M.H.-P., Asociación Canaria de Neumología y Cirugía Torácica (NEUMOCAN), and an agreement between the Spanish Ministry of Science, Innovation and Universities and Universidad de La Laguna. M.P.-Y. was also supported by a grant from the Ramón y Cajal Program (RYC-2015-17205) by MCIN/AEI/10.13039/501100011033 and by the European Social Fund “ESF Investing in your future.” J.P.-G. was funded by the fellowship FPU19/02175 (Formación Profesorado Universitario Program) from the Spanish Ministry of Universities. A.E.-O. reports funding from the Spanish Ministry of Science, Innovation, and Universities (MICIU) and Universidad de La Laguna (ULL), under the M-ULL program. Genotyping was performed at the Spanish National Cancer Research Centre, in the Human Genotyping lab, a member of CeGen, PRB3, and is supported by grant PT17/0019, of the PE I+D+i 2013-2016, funded by ISCIII and ERDF. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing the report. |
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| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
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| The summary statistics of differential bacterial genera abundance analyses are openly available in the Zenodo repository (https://doi.org/10.5281/zenodo.6062007). Demultiplexed sequencing reads of the 16S rRNA gene generated in this study (biological samples, mock communities, and negatives controls) are publicly available in the Sequence Read Archive (SRA) database under accession no. PRJNA878647. |
Vol 151 - N° 3
P. 706-715 - mars 2023 Retour au numéro
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