Advances in Biomedicine Research symposium

21 July 2025 - less than 1 min read time
Tags: Flash talk

Abstract

Background: Genetic variation regulates the abundance of bacteria from the upper airway microbiome linked to asthma exacerbations [1]. 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 [2]. DMRs were enriched in genes involved in lung inflammation (FDR=0.07), and DNA transcription regulation (FDR=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).

References

[1] Perez-Garcia, J., et al. J Allergy Clin Immunol. 2023, 152, 799-806

[2] Perez-Garcia, J., et al. J Allergy Clin Immunol. 2023, 151, 706-715