Pathogenic Mechanisms in C Diff Infection and Colitis

Pathogenic Mechanisms in Clostridium Difficile Infection and Colitis

The purpose of this study is to learn more about infection by Clostridium difficile (also known as C. difficile). C. difficile is a common bacterium (a germ that may cause disease) that can live in the human gut. Some people have it without having any symptoms. In other people it can cause illness ranging from mild diarrhea to severe colitis (infection of the colon).

C. difficile makes toxins that damage the cells that line the colon. The study doctors want to find out how these toxins cause damage to the cells in the colon.

The purpose of this study is to examine pathogenic mechanisms of Clostridium difficile toxin-mediated intestinal injury and inflammation. Two primary mechanisms will be examined.

• To examine the hypothesis is that microRNA expression profiles are dysregulated by Clostridium difficile toxin exposure and that dysregulation of miRNA expression plays a role in the pathogenesis of C. difficile associated diseases.
• To examine the hypothesis is that the TLR9 receptor mediates key inflammatory events in response to Clostridium difficile toxin exposure.

Inclusion Criteria:

• Age greater than 18 yrs and less than 75 years
• Undergoing a clinically indicated colonoscopy

Exclusion Criteria:

• Known, active or recurrent colonic disease including: Clostridium difficile infection, inflammatory bowel disease, microscopic colitis, colon resection for any reason, ischemic colitis, recurrent diverticulitis, colon cancer. Note: Diverticulosis without recurrent diverticulitis, colonic adenomatous or hyperplastic polyps or colonic arteriovenous malformations will not constitute an exclusion
• Diarrhea (an average of more than 3 bowel movements per day at baseline)
• Constipation (an average of fewer than 2 bowel movements per week at baseline).
• Use of systemic steroid or systemic immunosuppressive medication
• Severe renal impairment
• Relative contraindication to colon biopsy including a bleeding diathesis or anti-coagulant use. Note: nonsteroidal antiinflammatory drug or asprin use will not constitute a contra-indication.