Review article: Mycobacterium avium subsp paratuberculosis as one cause ofCrohn's disease

A number of theories regarding the aetiology of Crohn's disease have been p roposed. Diet, infections, other unidentified environmental factors and imm une disregulation, all working under the influence of a genetic predisposit ion, have been viewed with suspicion. Many now believe that Crohn's 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 paratubercu losis), the causative agent of Johne's disease, an inflammatory bowel disea se in a variety of mammals including cattle, sheep, deer, bison, monkeys an d chimpanzees. The evidence to support M. paratuberculosis infection as a c ause of Crohn's disease is mounting rapidly. Technical advances have allowe d the identification and/or isolation of M. paratuberculosis from a signifi cantly higher proportion of Crohn's disease tissues than from controls. The se methodologies include: (i) improved culture techniques; (ii) development of M. paratuberculosis-specific polymerase chain reaction assays; (iii) de velopment of a novel in situ hybridization method; (iv) efficacy of macroli de and anti-mycobacterial drug therapies; and (v) discovery of Crohn's dise ase-specific seroreactivity against two specific M. paratuberculosis recomb inant antigens. The causal role for M. paratuberculosis in Crohn's disease and correlation of infection with specific stratification(s) of the disorde r need to be investigated. The data implicating Crohn's as an autoimmune di sorder may be viewed in a manner that supports the mycobacterial theory. Th e mycobacterial theory and the autoimmune theory are complementary; the fir st deals with the aetiology of the disorder, the second deals with its path ogenesis. Combined therapies directed against a mycobacterial aetiology and inflammation may be the optimal treatment of the disease.