title: Diet-Microbiota Interactions Mediate Global Epigenetic Programming in Multiple Host Tissues.
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.
authors.affiliation: 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.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Krautkramer
authors.affiliation: Department of Bacteriology, University of Wisconsin - Madison, Madison, WI 53706, USA.
authors.forename: Julia H
authors.initials: JH
authors.lastname: Kreznar
authors.affiliation: Department of Bacteriology, University of Wisconsin - Madison, Madison, WI 53706, USA.
authors.forename: Kymberleigh A
authors.initials: KA
authors.lastname: Romano
authors.affiliation: Department of Bacteriology, University of Wisconsin - Madison, Madison, WI 53706, USA.
authors.forename: Eugenio I
authors.initials: EI
authors.lastname: Vivas
authors.affiliation: Biotechnology Center, University of Wisconsin - Madison, Madison, WI 53706, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Barrett-Wilt
authors.affiliation: Department of Biochemistry, University of Wisconsin - Madison, Madison, WI 53706, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Rabaglia
authors.affiliation: Department of Biochemistry, University of Wisconsin - Madison, Madison, WI 53706, USA.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Keller
authors.affiliation: Department of Biochemistry, University of Wisconsin - Madison, Madison, WI 53706, USA.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Attie
authors.affiliation: Department of Bacteriology, University of Wisconsin - Madison, Madison, WI 53706, USA. Electronic address: ferey@wisc.edu.
authors.forename: Federico E
authors.initials: FE
authors.lastname: Rey
authors.affiliation: 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.
authors.forename: John M
authors.initials: JM
authors.lastname: Denu
mesh_terms: D000273:Adipose Tissue / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D003106:Colon / Q000201:enzymology / Q000378:metabolism; D019175:DNA Methylation; D066273:Diet, Western; D044127:Epigenesis, Genetic; D005232:Fatty Acids, Volatile / Q000378:metabolism*; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity
chemical_list: D005232:Fatty Acids, Volatile; D006657:Histones
keywords: SCFA; epigenetic; gut microbiota; histone PTM; histone acetylation; histone methylation; histone proteomics; microbiome; short-chain fatty acid