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

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


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipose Tissue / enzymology
  • Adipose Tissue / metabolism
  • Animals
  • Colon / enzymology
  • Colon / metabolism
  • DNA Methylation
  • Diet, Western*
  • Epigenesis, Genetic*
  • Fatty Acids, Volatile / metabolism*
  • Gastrointestinal Microbiome / physiology*
  • Histones / genetics
  • Histones / metabolism
  • Liver / enzymology
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Organ Specificity


  • Fatty Acids, Volatile
  • Histones