Linking the gut microbiome to host DNA methylation by a discovery and replication epigenome-wide association study
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 (P<sub>meta-analysis</sub> = 3.21 × 10<sup>-11</sup>) and cg12234533 (P<sub>meta-analysis</sub> = 4.29 × 10<sup>-10</sup>). 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.
Authors
- Ayşe Demirkan (ORCID: https://orcid.org/0000-0002-7546-0867)
- Jingyuan Fu (ORCID: https://orcid.org/0000-0001-5578-1236)
- Marc Jan Bonder (ORCID: https://orcid.org/0000-0002-8431-3180)
- Soesma A. Jankipersadsing (ORCID: https://orcid.org/0000-0001-9225-9236)
- Erik A. Ehli (ORCID: https://orcid.org/0000-0002-7865-3015)
- Richard G. IJzerman (ORCID: https://orcid.org/0000-0001-7951-786X)
- Cisca Wijmenga (ORCID: https://orcid.org/0000-0002-5635-1614)
- Gonneke Willemsen (ORCID: https://orcid.org/0000-0003-3755-0236)
- Alexander Kurilshikov (ORCID: https://orcid.org/0000-0003-2541-5627)
- Harm-Jan Westra (ORCID: https://orcid.org/0000-0001-7038-567X)
- Alexandra Zhernakova (ORCID: https://orcid.org/0000-0002-4574-0841)
- Jenny van Dongen (ORCID: https://orcid.org/0000-0003-2063-8741)
- Eco J. C. de Geus (ORCID: https://orcid.org/0000-0001-6022-2666)
- Dorret Irene Boomsma (ORCID: https://orcid.org/0000-0002-7099-7972)
- Casey T. Finnicum (ORCID: https://orcid.org/0000-0001-5959-3961)
- Lude Franke
Institutions
- University Medical Center Groningen (NL)
- University of Groningen (NL)
- University of Surrey (GB)
- Amsterdam University Medical Centers (NL)
- Avera McKennan Hospital & University Health Center (US)
- Vrije Universiteit Amsterdam (NL)
Publication Details
- Journal
- BMC Genomics
- Published
- 2024-12-19
- DOI
- https://doi.org/10.1186/s12864-024-11136-x
- Citations
- 6
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 1.40