Gut microbes and the fatty acids they produce can regulate gene expression by influencing the 3D shape of their hosts' DNA.
Intestinal bacteria are known to affect several aspects of host health, including the risk of cardiovascular and metabolic diseases. To study the mechanisms by which this occurs, Federico Rey and John Denu at the University of Wisconsin–Madison and their colleagues compared mice raised with and without gut bacteria. They found that gut microbes mediate chemical changes to histone proteins, which in turn regulate gene expression by binding to DNA and altering its 3D conformation.
Feeding mice a high-fat, high-sugar diet provides little material for microbes to digest and so blocked some of the changes to DNA shape. Giving short-chain fatty acids (which are produced by gut microbes) to mice raised without gut bacteria restored these effects.
Mol. Cell http://doi.org/btr6 (2016)
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Gut microbes shape DNA. Nature 540, 11 (2016). https://doi.org/10.1038/540011e