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

Genome Biology

John D. Roberts¹  Yufeng Qin¹  Ruifang Li¹  Kaliopi Chrysovergis¹  Paul A. Wade¹  Sara A. Grimm²  Leesa J. Deterding³  Fred B. Lih³ 

[1] Eukaryotic Transcriptional Regulation Group, Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences;Integrative Bioinformatics Group, Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences;Mass Spectrometry Research & Support Group, Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences;

关键词: Microbiome;    Obesity;    Cancer;    Colorectal cancer;    Epigenetics;    Transcription factor;   

DOI  :  10.1186/s13059-018-1389-1

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown