Diet-Microbiota Interactions Mediate Global Epigenetic Programming in Multiple Host Tissues
Open accessAbstract
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.
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A lack of fermentable fiber in the diet results in reduced microbiota-driven production of short-chain fatty acids, which play an important role in both adaptive and innate immunity.
“a lack of fermentable fiber in the diet results in reduced microbiota-driven production of SCFAs, which are known to play an important role in both adaptive and innate immunity (Krautkramer et al., 2016).”
From Viral Infections, the Microbiome, and Probiotics (2021) · cites this paper as Krautkramer et al., 2016
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- Authors
- Krautkramer, K. A., Kreznar, J. H., Romano, K. A., Vivas, E. I., Barrett-Wilt, G. A., Rabaglia, M. E., Keller, M. P., Attie, A. D., Rey, F. E., & Denu, J. M.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Rey, Federico E.
- Denu, John M.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 64
- Issue
- 5
- Pages
- 982-992
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC5227652
- OpenAlex
- W2553615018
- Cited by
- 607
- References
- 54
- Citations by year
- 2026: 76 · 2025: 59 · 2024: 50 · 2023: 64 · 2022: 63 · 2021: 85 · 2020: 65 · 2019: 56 · 2018: 52 · 2017: 36 · 2016: 1
- FWCI
- 26.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (F30 DK108494, GM059789-15/P250VA, DK108259, DK101573)
- Clinical and Translational Science Award program through the NIH National Center for Advancing Translational Sciences (UL1TR000427, KL2TR000428)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- gut microbiota, diet, histone acetylation, histone methylation, chromatin modification, epigenetic programming, Western diet, short-chain fatty acids, germ-free mice, microbial colonization, histone-modifying enzymes
- MeSH terms
- Gastrointestinal Microbiome, Adipose Tissue, Animals, Colon, Fatty Acids, Volatile, Histones, Liver, Male, Mice, Inbred C57BL, Organ Specificity, DNA Methylation, Epigenesis, Genetic, Mice, Diet, Western
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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