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. 2024 Dec 19;25(1):1224.
doi: 10.1186/s12864-024-11136-x.

Linking the gut microbiome to host DNA methylation by a discovery and replication epigenome-wide association study

Ayşe Demirkan  1   2 , Jenny van Dongen  3   4 , Casey T Finnicum  5 , Harm-Jan Westra  6 , Soesma Jankipersadsing  6 , Gonneke Willemsen  3   4 , Richard G Ijzerman  7 , Dorret I Boomsma  4   8 , Erik A Ehli  5 , Marc Jan Bonder  6 , Jingyuan Fu  6   9 , Lude Franke  6 , Cisca Wijmenga  6 , Eco J C de Geus  3   4 , Alexander Kurilshikov  6 , Alexandra Zhernakova  10
Affiliations

Linking the gut microbiome to host DNA methylation by a discovery and replication epigenome-wide association study

Ayşe Demirkan et al. BMC Genomics. .

Abstract

Microbiome influences multiple human systems, but its effects on gene methylation is unknown. We investigated the relations between gene methylation in blood and the abundance of common gut bacteria profiled by 16s rRNA gene sequencing in two population-based Dutch cohorts: LifeLines-Deep (LLD, n = 616, discovery) and the Netherlands Twin Register (NTR, n = 296, replication). In LLD, we also explored microbial pathways using data generated by shotgun metagenomic sequencing (n = 683). Methylation in both cohorts was profiled in blood samples using the Illumina 450K array. Discovery and replication analysis identified two independent CpGs associated with the genus Eggerthella: cg16586104 (Pmeta-analysis = 3.21 × 10-11) and cg12234533 (Pmeta-analysis = 4.29 × 10-10). We also show that microbiome can mediate the effect of environmental factors on host gene methylation. In this first association study linking epigenome to microbiome, we found and replicated the associations of two CpGs to the abundance of genus Eggerthella and identified microbiome as a mediator of the exposome. These associations are observational and suggest further investigation in larger and longitudinal set-ups.

Keywords: 16s rRNA; DNA methylation; Gut microbiome; Host gene methylation; Shotgun-metagenomics.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The Lifelines protocol was approved by the UMCG Medical ethical committee under number 2007/152. The Netherlands Twin Register: The study was approved by the Central Ethics Committee on Research Involving Human Subjects of the VU University Medical Centre, Amsterdam, an Institutional Review Board certified by the U.S. Office of Human Research Protections (IRB number IRB00002991 under Federal-wide Assurance-FWA00017598; IRB/institute codes, NTR 03-180). Informed consent to participate was obtained from all of the participants in both Lifelines and NTR. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Schematic representation of the study
Fig. 2
Fig. 2
Mediation analysis of environmental exposures, microbiome and CpG methylation. Figure 2. Mediation analysis of environmental exposures, microbiome and CpG methylation. Pnominal represents the p-value of association of environmental exposure to microbial trait and CpG. Padjrepresents the conditional association of environmental exposure to both microbiome and methylation traits, adjusted for each other. Propmediatedrepresents the proportion of environmental effect on CpG methylation which is mediated by microbial trait. PACME represents the significance of Average Causal Mediation Effects (ACME).
See this image and copyright information in PMC

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