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

• Published in: BMC genomics Vol. 25; no. 1; pp. 1224 - 11
• Main Authors: Demirkan, Ayşe, van Dongen, Jenny, Finnicum, Casey T., Westra, Harm-Jan, Jankipersadsing, Soesma, Willemsen, Gonneke, Ijzerman, Richard G., Boomsma, Dorret I., Ehli, Erik A., Bonder, Marc Jan, Fu, Jingyuan, Franke, Lude, Wijmenga, Cisca, de Geus, Eco J. C., Kurilshikov, Alexander, Zhernakova, Alexandra
• Format: Journal Article
• Language: English
• Published: London BioMed Central 19.12.2024; BioMed Central Ltd; BMC
• Subjects: 16s rRNA; Adult; Animal Genetics and Genomics; Biomedical and Life Sciences; Blood; Care and treatment; Coffee; Composition; CpG Islands - genetics; Diagnosis; Diet; Disease; DNA biosynthesis; DNA Methylation; Environmental effects; Environmental factors; Epigenetics; Epigenome; Female; Gastrointestinal diseases; Gastrointestinal Microbiome - genetics; Gene sequencing; Genetics; Genome-Wide Association Study; Gut microbiome; Gut microbiota; Health aspects; Host gene methylation; Humans; Inflammatory bowel disease; Intestinal microflora; Kinases; Laxatives; Life Sciences; Male; Metabolism; Metagenomics; Methylation; Microarrays; Microbial Genetics and Genomics; Microbiomes; Microbiota (Symbiotic organisms); Microorganisms; Middle Aged; Netherlands; Plant Genetics and Genomics; Population studies; Proteomics; Replication; Risk factors; RNA, Ribosomal, 16S - genetics; rRNA 16S; Shotgun-metagenomics; Netherlands; DNA methylation; 16s rRNA; Shotgun-metagenomics; Host gene methylation; Gut microbiome
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/s12864-024-11136-x

Summary 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 meta−analysis = 3.21 × 10 −11 ) and cg12234533 (P meta−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.