XXXIX Congress of the Sociedad Canaria de Neumología y Cirugía Torácica (NEUMOCAN)
The blood epigenome is associated with nasal bacteria 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 influences the nasal microbiome associated with asthma exacerbations, yet the contribution of DNA methylation (DNAm) remains unknown. This study aimed to identify leukocyte epigenetic markers linked to nasal bacterial taxa related to asthma exacerbations.
Methods: Nasal and blood samples from 171 adults and 51 children of the GEMAS cohort were analyzed. DNA methylation was assessed using the Illumina EPICv1 array, and the nasal microbiome was profiled by 16S rRNA gene sequencing (V3–V4 regions). Epigenome- and microbiome-wide association studies were conducted to evaluate 709,923 CpG sites in relation to three alpha diversity indices (Observed, Shannon, and Faith) and twelve bacterial genera previously associated with asthma exacerbations. Results were meta-analyzed across age groups. Regression models were adjusted for age, sex, ancestry, and cell-type heterogeneity. Differentially methylated regions (DMRs) were identified and subjected to enrichment analyses. Multiple testing correction was performed using a false discovery rate (FDR) threshold of <0.05.
Results: Methylation at 31 CpG sites was significantly associated (FDR < 0.05) with the bacterial genera Dolosigranulum, Fusobacterium, Leptotrichia, Porphyromonas, and Streptococcus, as well as with the Faith and Observed diversity indices. Several associated CpGs mapped to genes previously implicated in asthma (OSBPL5, SIGLECP3, EXOC4). A total of 234 DMRs were associated with the 12 asthma-related genera and 103 DMRs with the three alpha diversity indices. The most significant DMRs were located in genes relevant to asthma and other pulmonary diseases (HOXB6: 3 CpGs, p = 4.2×10−9; ZBTB38: 5 CpGs, p = 9.1×10−17; TAGLN: 4 CpGs, p = 6.4×10−11; GNA12: 3 CpGs, p = 4.7×10−10; ZNF415: 5 CpGs, p = 3.5×10−13). Enrichment analysis revealed an overrepresentation of DMRs within the Wnt signaling pathway (adjusted p = 0.008). The Wnt pathway regulates inflammation, airway remodeling, and bronchial hyperreactivity, and has been proposed as a novel therapeutic target in asthma.
Conclusion: These novel associations between blood DNA methylation and nasal bacteria involved in asthma exacerbations suggest that host–microbiome interactions may influence the Wnt signaling pathway through epigenetic mechanisms.
Funding: Fundación DISA (009/2024), MCIN/AEI/10.13039/501100011033 (PID2020-116274RB-I00).