The three main findings of this study are as follows: (1) hCA I-specific oral tolerance was inducible in a murine model of IBD and inhibited the progression of murine experimental colitis by suppressing inflammatory cytokines in the MLNs; (2) Upon colitis worsening, the amount of fecal CA I decreases, and rectal supplementation with hCA I can reduce the severity of colitis; (3) hCA I had a non-inferior suppressive effect on colitis compared with established drugs (5-ASA or PSL) in a murine model of IBD. This evidence concerns the gene CA1 and inflammatory bowel disease.