Herein, we describe an anti-inflammatory role for colonic ANGPTL4 in dextran sulfate sodium salt (DSS)-induced colitis and dietary stearic acid (SA) intake in vitro and in vivo. We showed that the microbiota was similar between ANGPTL4+/+ and ANGPTL4−/− mice at steady states, but with perturbation such as DSS treatment some differences in microbiota community become accentuated. This evidence concerns the gene ANGPTL4 and colitis.