mouse gut microbiome. Mus musculus

Mammals have a complicated symbiotic relationship with their gut microbiome which is postulated to have broad impacts on host health and disease. Here, we profiled the gut microbiome and chromatin features at DNA cis-regulatory elements in colon epithelium from mice fed either an obesogenic or control diet. The obesogenic diet shaped the microbiome prior to the development of obesity, leading to altered bacterial metabolite production which predisposes the host to obesity. This microbiota-diet interaction led to the alteration of chromatin features at host cis-regulatory loci associated with signaling pathways integral to colon cancer. In microbiome transfer into germ free mice, recapitulation of the host enhancer signature resembling cancer required both an obesogenic diet and its associated microbiome. These findings suggest that bacterial metabolism of the host diet programs the enhancer landscape in the colon, with downstream impacts on host metabolism and disease risk.