Butyrate, IL-4, and EP4 Receptors: A Triad of Colorectal Homeostasis, Protecting Against Onset of Cancer and IBD?

In this article, onset mechanisms of colorectal cancer and intestinal bowel diseases (IBD) are postulated to involve the aberrant expression/hyper-activation of E-type prostanoid 4 (EP4) receptors. Although prostaglandin E and EP4 receptors are important factors for maintaining colorectal homeostasis, their mediated signaling is also considered to be involved in the etiology of severe intestinal diseases. To prevent uncontrollable activations of EP4 receptors, two safety factors are proposed: butyrate as an external safety factor and interleukin (IL)-4 as an internal safety factor. Thus, for maintaining vulnerable colorectal homeostasis, the levels of EP4 receptors, butyrate, and IL-4 are proposed as an important triad for protecting against development/onset risks of, at least, EP4 receptor-mediated cancer and IBD.