Preprint Linking the gut microbiome to host DNA methylation by a discovery and replication epigenome-wide association study, 2023, Demirkan et al.

[SNT Gatchaman]

Linking the gut microbiome to host DNA methylation by a discovery and replication epigenome-wide association study
Ayse Demirkan; Jenny van Dongen; Casey Finnicum; Harm Jan Westra; Soesma Jankipersadsing; Gonneke Willemsen; Richard Ijzerman; Dorret Boomsma; Erik Ehli; Mark Jan Bonder; Jingyuan Fu; Lude Franke; Cisca Wijmenga; Eco de Geus; Alexander Kurilshikov; Alexandra Zhernakova

Both gene methylation and the gut microbiome are partially determined by host genetics and partially by environment.

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: LifeLinesDeep (LLD, n = 616, discovery) and the Netherlands Twin Register (NTR, n = 296, replication). In LLD, we also explored microbiome composition using data generated by shotgun metagenomic sequencing (n = 683). We then investigated if genetic and environmental factors can explain the methylation and microbiota associations in a set of 78 associated CpG x taxa pairs from the EWAS meta analysis. In both cohorts, blood and stool samples were collected within 2 weeks of each other. Methylation was profiled in blood samples using the Illumina 450K array. Methylation and microbiome analysis pipelines were harmonized across cohorts. Epigenome wide association study (EWAS) of microbial features were analysed using linear regression with adjustment for technical covariates.

Discovery and replication analysis using 16s data identified two independent CpGs associated with the genus Eggerthella: cg16586104 (Pmeta analysis = 3.21e-11) and cg12234533 (Pmeta analysis = 4.29e-10). While we did not find human genetic variants that could explain the associated CpG x taxa/pathway pairs, we show that microbiome can mediate the effect of environmental factors on epigenetics.

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.


Link | PDF (Preprint: BioRxiv)

 

[SNT Gatchaman]

CpG methylation: see Wikipedia entry.

We performed an association study between the gut microbiome and host epigenome in 912 individuals from two independent Dutch cohorts.

We identified study-wide association of CpG methylation with one bacterial taxa, Eggerthella, which was associated with two independent CpGs. Exploring the effect of environmental factors on the microbiome and methylation identified that for a subset of associations the same exposome factors – coffee consumption, dairy intake and use of laxatives, PPIs and antidepressants – are associated to both the microbiome and methylation. We also show a potential role for three bacterial taxa in mediating the effects of coffee, SSRI antidepressants and laxatives on DNA methylation

Genus Eggerthella is one of the gut microbiome genera we found to be associated with methylation in blood. Eggerthella is part of the normal human intestinal microbiome and has been most commonly associated with infections spreading from the gastrointestinal tract, but it has also been found interacting with food intake while influencing metabolism of drugs. This genus has also been shown to be more abundant in individuals with psychiatric diseases and higher grade neoplasms.