Advances in Biomedicine Research (ABRE) symposium
Association of the blood epigenome with the upper airway microbiome involved in asthma exacerbations
Erick Castillo-Vargas, MSc1, Mario Martin-Almeida, MSc1, Elena Martin-Gonzalez, MSc1, Ruperto González-Pérez, MD, PhD2, José M. Hernández-Pérez, MD, PhD3,4, Olaia Sardón-Prado, MD, PhD5,6, Paloma Poza-Guedes, MD, PhD2, 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, Fabian Lorenzo-Diaz, PhD1, Maria Pino-Yanes, PhD1,8,13, 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 Severe Asthma Unit, Allergy Department, Hospital Universitario de Canarias, La Laguna, Tenerife, Spain.
3 Pulmonary Medicine Service, Hospital Universitario de N.S de Candelaria, La Laguna, Tenerife, Spain.
4 Pulmonary Medicine Section, Hospital Universitario de La Palma, La Palma, 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 Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna (ULL), La Laguna, Tenerife, Spain.
Background: Genetic variation regulates the abundance of bacteria from the upper airway microbiome linked to asthma exacerbations. However, the role of DNA methylation (DNAm) remains unclear. We aimed to identify leukocyte epigenetic markers associated with upper airway bacterial genera involved in asthma exacerbations.
Methods: The pharyngeal and nasal microbiome were analyzed in up to 176 Canary Islanders with asthma by 16S rRNA (V3-V4 regions) sequencing. The blood epigenome was analyzed using the Illumina EPICv1 array. Associations between 709,923 CpGs and microbiome traits were examined through epigenome-wide testing adjusted for age, sex, ancestry, and cell heterogeneity. Differentially methylated regions (DMRs) were identified and subjected to enrichment analysis. Multiple testing was adjusted using a false discovery rate (FDR)<0.1.
Results: DNAm at six CpG sites, involving the genes GRIN2D, TCF4, LRRC4C, UGDH, and ZNF331, were significantly associated with pharyngeal Campylobacter abundance (p<5x10-7) and one CpG (LOC101927284) was significantly associated with nasal Dolosigranulum abundance (p=8.9x10-8). 249 and 336 DMRs were associated with exacerbation-related pharyngeal and nasal bacterial genera, respectively, previously identified in this cohort. DMRs were enriched in genes involved in lung inflammation (adjusted p=0.07), and DNA transcription regulation (adjusted p=3.69x10-6).
Conclusion: We reported novel associations between leukocyte methylation at DNA regulatory transcription loci and pulmonary inflammation-related genes and the upper airway microbiome involved in asthma exacerbations. These findings highlight the potential of epigenetic regulation as a mediator of host–microbiome crosstalk in asthma pathogenesis.
Funding: Fundación DISA (009/2024), MCIN/AEI/10.13039/501100011033 (PID2020-116274RB-I00).