How Gut Bacteria Shape Our Genes Through Fiber

Scientists have long observed that eating more dietary fiber is linked to a healthier gut and a lower risk of diseases like colorectal cancer. A new study in Nature Metabolism explored the mechanism behind this link in both cell cultures and mice. The researchers looked at what happens when fiber is broken down by gut bacteria. When gut bacteria degrade fibers, short-chain fatty acids (SCFAs), including butyrate and propionate are produced. These metabolites act as histone deacetylase inhibitors, leading to the addition of chemical “tags” (acetyl groups) on proteins called histones, which package DNA. The placement of these tags changes how tightly DNA is wrapped and makes certain genes easier to access. This process directly influenced genes involved in cell growth, repair of the gut lining, communication with the immune system, and the regulation of pathways that are often disrupted in cancer.

The scientists found that both propionate and butyrate created a distinct type of histone tag. Propionate installed propionylation, while butyrate installed butyrylation, and both occurred at very specific sites on the histone proteins. These changes loosened the packaging of DNA, making it possible for the cell’s transcription machinery to access sections that would otherwise be hidden. As a result, not only were individual genes switched on, but entire gene networks were rewired. In other words, the SCFAs reset the cell’s genetic “program,” shifting the balance of how many groups of genes worked together. In human colon cancer cells, this meant large coordinated changes in gene activity, which scientists tracked using sequencing and imaging technologies. These findings provide a mechanistic explanation of how gut microbial products can reshape the fundamental instructions of a cell.

To test whether these effects occurred outside the lab dish, the team turned to mice. Animals fed with a high-fiber diet had higher levels of SCFAs in their intestines, and their gut lining showed the same histone modifications as observed in the cell experiments. This indicates that the mechanism also works in living organisms consuming a high-fiber diet. Still, the study did not measure disease outcomes such as tumor prevention or improved gut health. Instead, it mapped the biological chain of events:

Dietary fiber is metabolized by gut bacteria, producing short-chain fatty acids (SCFAs). The SCFAs can act as signaling molecules and inhibitors of histone deacetylases (HDACs), leading to changes in histone acetylation. Altered histone states influence chromatin structure and thereby modulate the activity of large networks of genes.

From a nutrition perspective, this highlights fiber as the starting point for a microbial process that sends powerful chemical signals to our cells, influencing how genetic information is read and potentially shaping long-term gut health.

‍