New way to alter DNA, affect health circumvents gut bacteria

Our gut microbiome helps us out every day by processing the fiber we can’t digest. The bacteria ferment the fiber into key chemicals known as short-chain fatty acids, or SCFAs, that are essential for human health. SCFAs fight inflammation, help kill dangerous bacteria, protect the lining of the gut, and can even help prevent cancer.

In a new study, CMB trainer John Denu and recent CMB graduate Sydney Thomas with the University of Wisconsin–Madison’s Wisconsin Institute for Discovery have learned that the fatty acids butyrate and propionate also activate p300, a crucial human enzyme that promotes the unspooling of DNA. This unwound DNA allows more genes to become active and expressed, which ultimately affects human health.

Previous research had suggested that SCFAs might instead contribute to this process by inhibiting a different set of enzymes.

This new understanding opens the possibility of activating p300 in a diet-dependent way or even independently of the microbiome. Knowing how to target p300 is vital because it is implicated in a wide variety of physiological processes and diseases, such as propionic acidemia, autism spectrum disorder, and Alzheimer’s disease.

“Knowing that butyrate and propionate directly interact with this protein opens up a lot of new areas of research that we didn’t even think to look at before, because we thought that it was happening the opposite way than it actually is,” says Sydney Thomas, a Denu lab graduate student and co-author on the paper.

Thomas and Denu, a professor of biomolecular chemistry, published their findings Oct. 22 in the journal eLife.

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