The Present Status of Antibiotic Therapy in Crohn’s Disease

Crohn’s disease (CD) is a disorder of the immune system leading to persistent inflammation and ulceration that may occur anywhere in the gastrointestinal tract, from mouth to anus. The etiology of CD is unknown but the disease is believed to manifest from a combination of factors which include genetic predisposition, immune dysregulation and environmental triggers. The interplay of these factors likely lead to a pathway of persistent gastrointestinal mucosal ulceration. Several pieces of evidence reveal the microbial rich intestinal environment likely plays a critical role in the development of CD. For many years various animal models of colitis revealed that a sterile environment would lead to quiescent disease and introducing commensal bacteria to the gastrointestinal tract would lead to the development of active colitis. Several scientists have also reported that diverting the fecal stream away from the area of active disease helps heal CD. More recently it is believed that a pivotal factor may be the innate immune system’s inability to clear microbial antigens, leading to an overactive adaptive immune response. The identification of the NOD2/CARD15 genetic mutation has strengthened the intricate interplay between the intestinal microbial environment and immune system. NOD2/CARD15 gene mutation is found more frequently in subjects with CD and involved in the expression of an intracellular receptor that senses muramyl dipeptide, a peptidoglycan component of gram-positive bacteria. Activation of NOD2 leads to activation of NF-κB which mediates transcription of numerous pro-inflammatory cytokines. A mutaINFLAMMATORY BOWEL DISEASE: A PRACTICAL APPROACH, SERIES #57