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Biological Chemistry

Diet and microbiome conspire to modify epigenetics

Short-chain fatty acids produced by the mouse microbiome in response to diet alter acetylation and methylation on histone proteins

by Sarah Everts
November 27, 2016 | APPEARED IN VOLUME 94, ISSUE 47

Over the past decade, scientists studying the human microbiome have found that the microorganisms inhabiting our bodies can influence our propensity for obesity, cardiovascular disease, diabetes, inflammatory bowel disease, and many other ailments. Although the precise mechanisms by which our microbiome alters our health—for good and bad—have mostly eluded researchers, many increasingly believe that the short-chain fatty acids produced by our microbes, including acetate, propionate, and butyrate, are likely involved.

Now a team of researchers led by Federico E. Rey and John M. Denu at the University of Wisconsin, Madison, reports that short-chain fatty acids produced by a mouse’s gut microbiome can affect the epigenetics in the animal’s cells: The compounds change the activity of enzymes that help add acetyl and methyl groups to histone proteins, thereby altering the availability of nearby DNA for transcription (Mol. Cell. 2016, DOI: 10.1016/j.molcel.2016.10.025). Although they found a direct connection between short-chain fatty acids and histone acetylation, the connection with histone methylation was less straightforward, suggesting that other microbiome metabolites are likely involved in modifying mouse epigenetics.

Furthermore, the team found that feeding mice a high-fat Western diet suppressed production of short-chain fatty acids by their gut microbes as well as the epigenetic modifications that would normally occur with a healthier fiber-rich diet.

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