Importantly, we provide the first direct mechanistic evidence that the effect of RF on the severity of IBD is directly gated by the intestinal clock because RF fails to reduce the inflammatory phenotype (immune cell infiltration, inflammatory marker gene expression, histopathological scores) when the intestinal clock is genetically dysfunctional in Bmal1IEC−/−xIL-10−/− mice. Here, CLOCK is linked to inflammatory bowel disease.