Inflammatory bowel disease: the role of environmental factors.

Environmental factors are essential components of the pathogenesis of inflammatory bowel disease (IBD) and primarily responsible for its growing incidence around the globe. Epidemiological, clinical and experimental evidence support an association between IBD and a large number of seemingly unrelated environmental factors, which include smoking, diet, drugs, geographical and social status, stress, microbial agents, intestinal permeability and appendectomy. Data supporting the involvement of each of these factors in predisposing to, triggering, or modulating the course or outcome of IBD vary from strong to tenuous. Smoking and the enteric bacterial flora are the ones for which the most solid evidence is currently available. Smoking increases the risk of Crohn's disease (CD) and worsens its clinical course, but has a protective effect in ulcerative colitis (UC). Presence of enteric bacteria is indispensable to develop gut inflammation in most animal models of IBD, and modulation of the quantity or quality of the flora can be beneficial in patients with IBD. Surprisingly, evidence for a major role of the diet in inducing or modifying IBD is limited, while that for nonsteroidal anti-inflammatory drugs is more convincing than for oral contraceptives. Northern geographic location, and a high social, economical, educational or occupational status increase the risk of IBD, an observation fitting the hygiene hypothesis for allergic and autoimmune diseases. Stress is also associated with IBD, but more as a modifier than an inducing factor, and its contribution is more obvious in IBD animal models than human IBD. Finally, an increased intestinal permeability may increase the risk for developing CD, whereas an appendectomy lowers the risk of developing UC.