Journal Article

An obesity-associated gut microbiome reprograms the intestinal epigenome and leads to altered colonic gene expression

Qin, Yufeng, Lih, Fred B., Roberts, John D., Li, Ruifang, Chrysovergis, Kaliopi, Deterding, Leesa J., Grimm, Sara A., Wade, Paul A.

2018

Overview

Background The gut microbiome, a key constituent of the colonic environment, has been implicated as an important modulator of human health. The eukaryotic epigenome is postulated to respond to environmental stimuli through alterations in chromatin features and, ultimately, gene expression. How the host mediates epigenomic responses to gut microbiota is an emerging area of interest. Here, we profile the gut microbiome and chromatin characteristics in colon epithelium from mice fed either an obesogenic or control diet, followed by an analysis of the resultant changes in gene expression. Results The obesogenic diet shapes the microbiome prior to the development of obesity, leading to altered bacterial metabolite production which predisposes the host to obesity. This microbiota–diet interaction leads to changes in histone modification at active enhancers that are enriched for binding sites for signal responsive transcription factors. These alterations of histone methylation and acetylation are associated with signaling pathways integral to the development of colon cancer. The transplantation of obesogenic diet-conditioned microbiota into germ free mice, combined with an obesogenic diet, recapitulates the features of the long-term diet regimen. The diet/microbiome-dependent changes are reflected in both the composition of the recipient animals’ microbiome as well as in the set of transcription factor motifs identified at diet-influenced enhancers. Conclusions These findings suggest that the gut microbiome, under specific dietary exposures, stimulates a reprogramming of the enhancer landscape in the colon, with downstream effects on transcription factors. These chromatin changes may be associated with those seen during colon cancer development.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Acetylation / Animal Genetics and Genomics / Animals / Bacteria / Bioinformatics / Biomedical and Life Sciences / Cancer / carcinogenesis / Cardiovascular disease / Chromatin / colon / Colon - metabolism / Colon cancer / Colorectal cancer / colorectal neoplasms / Diabetes / Diet / Digestive system / enhancer elements / Enhancer Elements, Genetic / Enhancers / Environmental effects / Epigenesis, Genetic / Epigenetics / epigenome / Epithelium / Epithelium - metabolism / Evolutionary Biology / Fatty acids / Female / Females / Gastrointestinal Microbiome - genetics / Gastrointestinal tract / Gene expression / Hepatocyte Nuclear Factor 4 - metabolism / histone code / histones / Human Genetics / human health / Inflammatory bowel disease / Intestinal microflora / intestinal microorganisms / Intestine / Life Sciences / Male / Males / Metabolites / methylation / Mice, Inbred C57BL / Microbial Genetics and Genomics / Microbiome / Microbiomes / Microbiomes and Metagenomics / Microbiota / Obesity / Obesity - genetics / Obesity - metabolism / Obesity - microbiology / obesogenic diet / Phenotype / Physiology / Plant Genetics and Genomics / Sexes / Transcription factor / Transcription factors / Transcriptome / Transplantation