Ion transport and epithelial barrier dysfunction in experimental models of ulcerative colitis.

The global prevalence of ulcerative colitis (UC) and Crohn's disease (CD) is increasing, placing greater burdens on national health systems. The pathophysiology of diarrhea, the commonest debilitating symptom in patients with UC and CD, has been studied more extensively in UC, where it reflects defective colonic Na+ absorption combined with changes in colonic Cl- and K+ transport, which significantly reduce colonic water absorption. Dysfunctional ion transport in patients with UC is accompanied by abnormalities in tight junctional protein distribution and function, which cause the inflamed colonic epithelium to become "leakier." Progress in understanding how abnormal colonic ion transport in UC might be influenced pharmacologically has been hampered by the low availability of clinical material. To counter this, various animal models of acute colitis have been developed, but differ in the way mucosal inflammation is induced. Identifying models that closely mimic human UC in terms of pathology and ion transport abnormalities remains challenging. However, the introduction of human colonic epithelial organoids (colonoids) has added a new and exciting dimension to research in this area. Here, we review current knowledge about abnormal colonic ion transport and barrier function in experimental and human colitis as well as the use and potential of human colonoids to better understand the pathophysiology of UC, which may ultimately lead to novel approaches to the treatment of diarrhea in this disease.