KRT8 and colonic disorder: Using the keratin-deficient intestinal epithelial specific K8 knockout model developed here, we report that loss of K8 only in these cells leads to major colonic disease phenotypes including: (i) partial loss of colonic epithelium, (ii) compromised intestinal barrier and diarrhea, (iii) increased metabolic activity and (iv) a modest colonic inflammation, which is more pronounced in aging mice.