Several experimental studies have investigated the therapeutic potential of PTX in models of colitis; however, the present study is the first to elucidate its modulatory effects on the SPHK1/S1P, IL‐6/STAT3, AMPK/mTOR/NLRP3, and ZO‐1 signaling pathways in experimental colitis. This evidence concerns the gene SPHK1 and colitis.