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Metabolic programming of the epigenome: host and gut microbial metabolite interactions with host chromatin

Published:August 30, 2017DOI:https://doi.org/10.1016/j.trsl.2017.08.005
      The mammalian gut microbiota has been linked to host developmental, immunologic, and metabolic outcomes. This collection of trillions of microbes inhabits the gut and produces a myriad of metabolites, which are measurable in host circulation and contribute to the pathogenesis of human diseases. The link between endogenous metabolite availability and chromatin regulation is a well-established and active area of investigation; however, whether microbial metabolites can elicit similar effects is less understood. In this review, we focus on seminal and recent research that establishes chromatin regulatory roles for both endogenous and microbial metabolites. We also highlight key physiologic and disease settings where microbial metabolite-host chromatin interactions have been established and/or may be pertinent.

      Abbreviations:

      α-KG (alpha-ketoglutarate), acetyl-CoA (acetyl coenzyme A), BBB (blood brain barrier), bSCFA (branched short chain fatty acid), CoA (coenzyme A), ConvD (conventionalized), ConvR (conventionally raised), CRC (colorectal cancer), DNMT (DNA methyltransferase), GF (germ-free), HAT (histone acetyltransferase), HDAC (histone deacetylase), HDACi (histone deacetylase inhibitor), HMT (histone methyltransferase), IBA (interbout arousal), LC-MS/MS (liquid chromatography coupled to tandem mass spectrometry), MACs (microbial accessible carbohydrates), NAFLD (nonalcoholic fatty liver disease), PTMs (post-translational modifications), SCFA (short chain fatty acid), T2DM (type 2 diabetes mellitus), TPN (total parenteral nutrition)
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