Mycobacterium avium subsp. paratuberculosis as one cause of Crohn’s disease

Authors

  • W. Chamberlin,

    1. Department of Medicine, William Beaumont Army Medical Center, El Paso, Texas, USA
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  • D. Y. Graham,

    1. Department of Medicine, Baylor College of Medicine, and Veterans Affairs Medical Center, Houston, Texas, USA
    2. Division of Molecular Virology, Baylor College of Medicine, and Veterans Affairs Medical Center, Houston, Texas, USA
    3. Inflammatory Bowel Disease Laboratory, Baylor College of Medicine, and Veterans Affairs Medical Center, Houston, Texas, USA
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  • K. Hulten,

    1. Department of Medicine, Baylor College of Medicine, and Veterans Affairs Medical Center, Houston, Texas, USA
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  • H. M. T. El-Zimaity,

    1. Department of Medicine, Baylor College of Medicine, and Veterans Affairs Medical Center, Houston, Texas, USA
    2. Department of Pathology, Baylor College of Medicine, and Veterans Affairs Medical Center, Houston, Texas, USA
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  • M. R. Schwartz,

    1. Department of Pathology, Baylor College of Medicine, and Veterans Affairs Medical Center, Houston, Texas, USA
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  • S. Naser,

    1. Department of Molecular Biology and Microbiology, University of Central Florida, Orlando, Florida, USA
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  • I. Shafran,

    1. Department of Molecular Biology and Microbiology, University of Central Florida, Orlando, Florida, USA
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  • F. A. K. El-Zaatari

    1. Department of Medicine, Baylor College of Medicine, and Veterans Affairs Medical Center, Houston, Texas, USA
    2. Inflammatory Bowel Disease Laboratory, Baylor College of Medicine, and Veterans Affairs Medical Center, Houston, Texas, USA
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Dr F. A. K. El-Zaatari, V.A. Medical Center (111D). 2002 Holcombe Blvd, Houston, TX 77030, USA. E-mail: fouade@bcm.tmc.edu

Abstract

A number of theories regarding the aetiology of Crohn’s 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’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 paratuberculosis), the causative agent of Johne’s 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’s disease is mounting rapidly. Technical advances have allowed the identification and/or isolation of M. paratuberculosis from a significantly higher proportion of Crohn’s 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 anti-mycobacterial drug therapies; and (v) discovery of Crohn’s disease-specific seroreactivity against two specific M. paratuberculosis recombinant antigens. The causal role for M. paratuberculosis in Crohn’s disease and correlation of infection with specific stratification(s) of the disorder need to be investigated. The data implicating Crohn’s 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.

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