As environmental factors play an outsized role in the development of inflammatory conditions (such as inflammatory bowel disease), epigenetic mechanisms likely play a crucial role in their pathology . Researchers led by a duo of (German Cancer Research Center, Heidelberg, Germany) and (Hebrew University Medical School, Jerusalem, Israel) also understood that the gut microbiome held the potential to modify the epigenetic landscape of specific intestine-resident cells, which would impact gene expression and intestinal cell function, key to maintaining intestinal homeostasis and avoiding disease development. Their recently published study explores how the gut microbiome impacts the epigenetic landscape of intestinal epithelial cells. These gut guardians provide a physical and biochemical barrier to segregate host tissue and the gut bacteria to maintain intestinal homeostasis , under normal conditions and in response to the acute inflammation associated with inflammatory bowel disease. Excitingly, their findings suggest that the activities of the gut microbiome support the generation of a specific epigenetic profile at the regulatory elements of intestinal health-associated genes. The authors hypothesize that this mechanism may help to support a gene expression profile that supports intestinal homeostasis and may also protect against the consequence of gut inflammation.