II Early Career Investigators' Congress on Bio-Organic Research

04 June 2025 - less than 1 min read time
Tags: Flash talk

Abstract

Background: Genetic variation influences the salivary microbiome associated with asthma exacerbations [1], yet the contribution of DNA methylation (DNAm) is unknown. The study aimed to identify leukocyte epigenetic markers linked to salivary bacterial taxa implicated in asthma exacerbations.

Methods: We analyzed saliva and blood samples from 197 patients from the GEMAS study. The salivary microbiome was profiled by 16S-rRNA gene sequencing (V3-V4 regions) and the blood methylome with the Illumina EPICv1 array. We conducted epigenome‐wide association analyses on 693,029 CpGs with diversity indices and 3 bacterial genera associated with asthma exacerbations in this cohort [2]. Models were adjusted for age, sex, ancestry, and tissue heterogeneity. We identified differentially methylated regions (DMRs) using dmrff and evaluated them in a pathway enrichment analysis using Enrichr. Multiple comparisons were adjusted using a false discovery rate (FDR)<0.05.

Results: DNAm levels at cg07977900 (RUBCN) were genome-wide significantly associated with Shannon diversity (p=3.2x10-8). We identified 117 DMRs associated with exacerbation‐related bacterial genera (Absconditabacteriales, Bifidobacterium, Capnocytophaga), and 126 DMRs with alpha diversity indices. Top‐hit DMRs were localized in major genes related to the histocompatibility complex (MHC) (PPP1R11: 14 CpGs, p=1.6x10-15; ATF6B: 33 CpGs, p=6.4x10-29; MPIG6B: 29 CpGs, p=2.1x10-31) and to a toll‐like receptor signaling gene (ZC3H12D: 13 CpGs, p=2.2x10-19). Enrichment analysis revealed overrepresentation of MHC protein complex genes (adjusted p=7.1x10-3).

Conclusion: Our findings showed novel associations between leukocyte DNAm at immune‐related loci and the salivary microbiome involved in asthma exacerbations, highlighting the role of the innate immune system in host-microbiome interactions.

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