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Mol Cell. 2016 Dec 1;64(5):982-992. doi: 10.1016/j.molcel.2016.10.025. Epub 2016 Nov 23.

Diet-Microbiota Interactions Mediate Global Epigenetic Programming in Multiple Host Tissues.

Author information

1
Wisconsin Institute for Discovery, Madison, WI 53715, USA; Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health - Madison, Madison, WI 53706, USA.
2
Department of Bacteriology, University of Wisconsin - Madison, Madison, WI 53706, USA.
3
Biotechnology Center, University of Wisconsin - Madison, Madison, WI 53706, USA.
4
Department of Biochemistry, University of Wisconsin - Madison, Madison, WI 53706, USA.
5
Department of Bacteriology, University of Wisconsin - Madison, Madison, WI 53706, USA. Electronic address: ferey@wisc.edu.
6
Wisconsin Institute for Discovery, Madison, WI 53715, USA; Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health - Madison, Madison, WI 53706, USA; Morgridge Institute for Research, Madison, WI 53715, USA. Electronic address: john.denu@wisc.edu.

Abstract

Histone-modifying enzymes regulate transcription and are sensitive to availability of endogenous small-molecule metabolites, allowing chromatin to respond to changes in environment. The gut microbiota produces a myriad of metabolites that affect host physiology and susceptibility to disease; however, the underlying molecular events remain largely unknown. Here we demonstrate that microbial colonization regulates global histone acetylation and methylation in multiple host tissues in a diet-dependent manner: consumption of a "Western-type" diet prevents many of the microbiota-dependent chromatin changes that occur in a polysaccharide-rich diet. Finally, we demonstrate that supplementation of germ-free mice with short-chain fatty acids, major products of gut bacterial fermentation, is sufficient to recapitulate chromatin modification states and transcriptional responses associated with colonization. These findings have profound implications for understanding the complex functional interactions between diet, gut microbiota, and host health.

KEYWORDS:

SCFA; epigenetic; gut microbiota; histone PTM; histone acetylation; histone methylation; histone proteomics; microbiome; short-chain fatty acid

PMID:
27889451
PMCID:
PMC5227652
DOI:
10.1016/j.molcel.2016.10.025
[Indexed for MEDLINE]
Free PMC Article

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