Transgenic mice (HBUS) that express the epidermal growth factor (EGFR) ligand HBEGF and a constitutively active G protein-coupled receptor (US28) in intestinal epithelial cells develop serrated polyps in the cecum. Development of serrated polyps depends on the composition of the gut microbiota and is associated with bacterial invasion of the lamina propria, accompanied by induction of inflammation and upregulation of interleukin 1 beta (IL1B) and matrix metalloproteinase 3 (MMP3) in the cecum. We investigated the mechanisms by which these changes contribute to development of serrated polyps.