IMFAHE International Conference 2026
Interactions Between the Host Epigenome and the Upper Airway Microbiome in Asthma Exacerbations
Erick Castillo-Vargas, MSc1,2, Mario Martin-Almeida, MSc1,2, Elena Martin-Gonzalez, MSc1,2, Ruperto González-Pérez, MD, PhD3, José M. Hernández-Pérez, MD, PhD4, Olaia Sardón-Prado, MD, PhD5,6, Paloma Poza-Guedes, MD, PhD3, Elena Mederos-Luis, MD7, Paula Corcuera-Elosegui, MD, PhD5, Inmaculada Sánchez-Machín, MD, PhD7, Leyre López-Fernández, MD5, Jesús Villar, MD, PhD8,9,10,11, Andres Cardenas, PhD12,13, Fabian Lorenzo-Diaz, PhD1, Maria Pino-Yanes, PhD1,2,8, Javier Perez-Garcia, PhD1,12
1 Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna (ULL), La Laguna, Tenerife, Spain.
2 Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna (ULL), La Laguna, Tenerife, Spain.
3 Severe Asthma Unit, Allergy Department, Hospital Universitario de Canarias, La Laguna, Tenerife, Spain.
4 Pulmonary Medicine Service, Hospital Universitario de N.S de Candelaria, La Laguna, Tenerife, Spain.
5 Division of Pediatric Respiratory Medicine, Hospital Universitario Donostia, San Sebastián, Spain.
6 Department of Pediatrics, University of the Basque Country (UPV/EHU), San Sebastián, Spain.
7 Allergy Department, Hospital Universitario de Canarias, La Laguna, Tenerife, Spain.
8 CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
9 Multidisciplinary Organ Dysfunction Evaluation Research Network (MODERN), Research Unit, Hospital Universitario Dr. Negrín, Las Palmas de Gran Canaria, Spain.
10 Faculty of Health Sciences, Universidad del Atlántico Medio, Tafira Baja, Las Palmas, Spain.
11 Li Ka Shing Knowledge Institute at the St. Michael’s Hospital, Toronto, Ontario, Canada.
12 Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, USA.
13 Department of Pediatrics, Stanford University School of Medicine, Stanford, USA.
Background: Asthma exacerbations are influenced by bacteria inhabiting our airways (microbiome). These microbial communities are shaped by both host genetics and environmental exposures. However, the role of epigenetics, which includes modifications such as DNA methylation (DNAm) that capture gene-environment interactions and regulate gene expression, remains unexplored. We hypothesized that human DNAm in blood is associated with airway bacteria involved in asthma exacerbations.
Methods: We studied 249 European adults and children with asthma, with available data of the nasal, pharyngeal, and saliva microbiomes and with blood DNAm levels at >731,000 positions across the genome (known as CpG sites). We conducted microbiome epigenome-wide association studies (mbEWAS) testing associations between 18 exacerbation-related bacteria and CpGs using statistical models corrected for confounders and multiple comparisons.
Results: We identified that DNAm at 59 CpGs were associated with microbial diversity and with the abundance of bacterial genera previously related to asthma exacerbations. Several of the strongest signals include genes involved in immune and inflammatory pathways relevant to asthma, suggesting potential therapeutic targets.
Conclusions: The first mbEWAS in asthma support the idea that asthma exacerbations may be influenced by microbiome-epigenome interactions, opening new avenues to better understand asthma and potentially improve future treatments.
Funding: MICIU/AEI/10.13039/501100011033 (PID2020-116274RB-I00), Fundación DISA (009/2024), Catalina Ruiz Program (ACIISI), FPU(FPU24/00854).