Review Article: Mycobacterium Avium Subsp. Paratuberculosis As One Cause Of Crohn\u27S Disease

A number of theories regarding the aetiology of Crohn\u27s disease have been proposed. Diet, infections, other unidentified environmental factors and immune disregulation, all working under the influence of a genetic predisposition, have been viewed with suspicion. Many now believe that Crohn\u27s disease is a syndrome caused by several aetiologies. The two leading theories are the infectious and autoimmune theories. The leading infectious candidate is Mycobacterium avium subspecies paratuberculosis (Mycobacterium paratuberculosis), the causative agent of Johne\u27s disease, an inflammatory bowel disease in a variety of mammals including cattle, sheep, deer, bison, monkeys and chimpanzees. The evidence to support M. paratuberculosis infection as a cause of Crohn\u27s disease is mounting rapidly. Technical advances have allowed the identification and/or isolation of M. paratuberculosis from a significantly higher proportion of Crohn\u27s disease tissues than from controls. These methodologies include: (i) improved culture techniques: (ii) development of M. paratuberculosis-specific polymerase chain reaction assays: (iii) development of a novel in situ hybridization method: (iv) efficacy of macrolide and antimycobacterial drug therapies: and (v) discovery of Crohn\u27s disease-specific seroreactivity against two specific M. paratuberculosis recombinant antigens. The causal role for M. paratuberculosis in Crohn\u27s disease and correlation of infection with specific stratification(s) of the disorder need to be investigated. The data implicating Crohn\u27s as an autoimmune disorder may be viewed in a manner that supports the mycobacterial theory. The mycobacterial theory and the autoimmune theory are complementary; the first deals with the aetiology of the disorder, the second deals with its pathogenesis. Combined therapies directed against a mycobacterial aetiology and inflammation may be the optimal treatment of the disease