Linking the gut microbiome to host DNA methylation by a discovery and replication epigenome-wide association study
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 (L...
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| Published in | BMC genomics Vol. 25; no. 1; pp. 1224 - 11 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
BioMed Central
19.12.2024
BioMed Central Ltd BMC |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1471-2164 1471-2164 |
| DOI | 10.1186/s12864-024-11136-x |
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| Abstract | 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. |
|---|---|
| AbstractList | 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 = 3.21 × 10.sup.-11) and cg12234533 (P.sub.meta-analysis = 4.29 × 10.sup.-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. 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. 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 = 3.21 × 10 ) and cg12234533 (P = 4.29 × 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. 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.sub.meta-analysis = 3.21 × 10.sup.-11) and cg12234533 (P.sub.meta-analysis = 4.29 × 10.sup.-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: Gut microbiome, Host gene methylation, DNA methylation, 16s rRNA, Shotgun-metagenomics 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. 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.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. 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 (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. |
| ArticleNumber | 1224 |
| Audience | Academic |
| Author | Fu, Jingyuan Wijmenga, Cisca Kurilshikov, Alexander Demirkan, Ayşe Ehli, Erik A. Franke, Lude van Dongen, Jenny Willemsen, Gonneke de Geus, Eco J. C. Finnicum, Casey T. Boomsma, Dorret I. Westra, Harm-Jan Bonder, Marc Jan Ijzerman, Richard G. Zhernakova, Alexandra Jankipersadsing, Soesma |
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Microbiome influences multiple human systems, but its effects on gene methylation is unknown. We investigated the relations between gene methylation in... Microbiome influences multiple human systems, but its effects on gene methylation is unknown. We investigated the relations between gene methylation in blood... Summary Microbiome influences multiple human systems, but its effects on gene methylation is unknown. We investigated the relations between gene methylation in... |
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| SubjectTerms | 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 |
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| Title | Linking the gut microbiome to host DNA methylation by a discovery and replication epigenome-wide association study |
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