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Microscopic colitis (MC) is the most common cause of watery diarrhea in the elderly. The condition is often treated with powerful medications that are expensive, and relapse is common after medications are stopped. Although the economic burden and impact on quality of life are considerable, the disease has been largely unstudied. Our goal in this application is to better understand disease characteristics, etiology and prognosis.

The term microscopic refers to the fact that the mucosa appears normal endoscopically. On microscopy, however, there is a lymphocytic infiltration of the surface epithelium (lymphocytic colitis) that may also be accompanied by a thickened collagen band (collagenous colitis). The collective term microscopic colitis refers to both collagenous and lymphocytic varieties that are considered to be different manifestations of the same disease.

The incidence of MC has generally been increasing and is now thought to be comparable to ulcerative colitis and Crohn’s disease. The etiology of MC is unknown. The disease is widely considered to be an abnormal immune reaction to luminal antigens in predisposed hosts. The concept of an luminal antigen is supported by the fact that the disease resolves with diversion of the fecal stream, and recurs when continuity is restored. Possible triggers are drugs, smoking, and autoimmunity. The drugs that have been implicated – NSAIDS, proton pump inhibitors and selective serotonin reuptake inhibitors, beta blockers and statins – belong to different classes but all serve as substrates for CYP2C19.

Although the incidence of MC is similar to inflammatory bowel disease, there are currently no NIH-funded studies of MC. Prior studies have been limited because of small size, questionable controls, inadequate exposure assessment, and narrow focus on one or a few risk factors.



  1. To quantitatively characterize microscopic colitis using image analysis microscopy. We hypothesize that there will considerable variation in the degree of lymphocytic infiltration that will correlate with etiology, symptoms and relapse.
  2. To investigate the etiology of microscopic colitis by examining medical and lifestyle risk factors. We will focus on whether medications, autoimmunity, diet, and smoking are associated with MC.
  3. To evaluate the association between the adherent microbial flora and MC. We hypothesize that the state of the microbial community is linked to the presence of MC.

As an exploratory aim we will determine whether polymorphisms of cytochrome P450 genes are more common in patients with presumed drug-induced MC. We hypothesize that polymorphisms in CYP2C19 will be more common among individuals with drug-induced MC.















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