Mechanisms and treatment of diarrhea in inflammatory bowel diseases

Diarrhea is one of the most common symptoms of patients with inflammatory bowel disease (IBD), having a reported frequency of 66-92% (1). Its frequency, severity, and metabolic effects are dependent on the degree, location, and extent of intestinal inflammation. Its presence and severity in IBD patients have served as useful indicators of disease activity and therapeutic response. To date, there are few specific treatments of IBD-associated diarrhea, in part because of the complexity and limited understanding of mechanisms. Physicians have largely resorted to treatments aimed at symptomatic control of diarrhea or at reducing the underlying inflammatory and immune processes. Unfortunately, many IBD patients, particularly those with severe disease, find the diarrhea especially debilitating and unpleasant, significantly affecting lifestyle and quality of life. In this review, we attempt to summarize the current understanding of causes of inflammation-associated diarrhea. Much of this information is derived from studies of experimental models of colitis and diarrhea and from in vitro models of established intestinal cell lines where specific pathophysiological processes can be studied. Thus, the relative importance of many of these potential diarrheal mechanisms in IBD cannot be presently ascertained and await additional studies in this area. However, some liberty has been taken to distill this information to create a conceptual framework for explaining how diarrhea develops in patients with inflammatory bowel diseases and how it can be treated.