SENP Congress 2026
Study of the interaction between the epigenome and the microbiome linked to asthma exacerbations in a Spanish pediatric population
Olaia Sardón-Prado, MD, PhD1,2*, Erick Castillo-Vargas, MSc3,4*, Mario Martin-Almeida, MSc3,4, Elena Martin-Gonzalez, MSc3,4, Paula Corcuera-Elosegui, MD, PhD1, Leyre López-Fernández, MD1, Fabian Lorenzo-Diaz, PhD3, Maria Pino-Yanes, PhD3,4,5, Javier Perez-Garcia, PhD3,6
1 Division of Pediatric Respiratory Medicine, Hospital Universitario Donostia, San Sebastián, Spain.
2 Department of Pediatrics, University of the Basque Country (UPV/EHU), San Sebastián, Spain.
3 Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna (ULL), La Laguna, Tenerife, Spain.
4 Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna (ULL), La Laguna, Tenerife, Spain.
5 CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
6 Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, USA.
* These authors share first authorship.
Background and objective: Genetic variation influences the respiratory microbiome associated with asthma exacerbations, but the role of DNA methylation remains unknown. This study aimed to identify blood epigenetic markers in children associated with airway bacteria involved in exacerbations.
Methods: We analyzed nasal, pharyngeal, salivary, and blood samples from 52 children recruited at Hospital Universitario Donostia (GEMAS study). DNA methylation was assessed using the Illumina EPICv1 array, and the microbiome was characterized through 16S rRNA gene sequencing. Association analyses were performed between methylation at 731,223 CpGs and three diversity indices and 18 bacterial genera, adjusting for confounders. Differentially methylated regions (DMRs) were identified and subjected to enrichment analysis, applying a false discovery rate (FDR)<0.1.
Results: Methylation at 5 CpGs was associated with the abundance of the genera Fusobacterium and Bifidobacterium (FDR<0.05). Three of these CpGs corresponded to genes potentially involved in asthma pathophysiology (FOXA2, TMX1, FRMD6-AS2). A total of 275 DMRs associated with the respiratory microbiome were identified (FDR<0.1), showing an overrepresentation of genes involved in the Wnt signaling pathway. This pathway regulates processes related to inflammation, airway remodeling, and bronchial hyperresponsiveness, and has been proposed as a potential therapeutic target for asthma.
Conclusion: We identified novel associations between blood DNA methylation and the respiratory microbiome linked to asthma exacerbations, highlighting potential biomarkers for the treatment of pediatric exacerbations.
Funding: Fundación DISA (009/2024); Programa Catalina Ruiz (ACIISI); MICIU/AEI/10.13039/501100011033, FEDER, UE (PID2024-160302OB-I00); FPU (FPU24/00854).