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

Area of Science:

• Human microbiome research
• Epigenetics and gene regulation
• Population-based cohort studies

Background:

• The human microbiome plays a crucial role in various physiological systems.
• The impact of the gut microbiome on host gene methylation remains largely unexplored.
• Understanding microbiome-epigenome interactions is vital for human health research.

Purpose of the Study:

• To investigate the relationship between gut bacteria abundance and gene methylation patterns in human blood.
• To identify specific microbial taxa associated with DNA methylation changes.
• To explore the potential mediating role of the microbiome in environmental factor effects on epigenetics.

Main Methods:

• Utilized 16S rRNA gene sequencing to profile gut bacteria in two Dutch cohorts (LifeLines-Deep and Netherlands Twin Register).
• Employed shotgun metagenomic sequencing in the LifeLines-Deep cohort to analyze microbial pathways.
• Assessed blood DNA methylation using the Illumina 450K array in both cohorts.

Main Results:

• Identified and replicated significant associations between two specific CpGs (cg16586104 and cg12234533) and the abundance of the bacterial genus Eggerthella.
• P-values for the meta-analysis were 3.21 × 10^-11 for cg16586104 and 4.29 × 10^-10 for cg12234533.
• Demonstrated that the microbiome can act as a mediator for the influence of environmental factors on host gene methylation.

Conclusions:

• This study provides the first evidence linking the human epigenome to the microbiome, with replicated associations found for Eggerthella.
• The findings suggest the gut microbiome's role in mediating the exposome's impact on host gene methylation.
• Further longitudinal studies with larger cohorts are warranted to confirm these observational findings.