Crohn's disease and the mycobacterioses: a review and comparison of two disease entities

Abstract

Crohn's disease is a chronic granulomatous ileocolitis, of unknown etiology, which generally affects the patient during the prime of life. Medical treatment is supportive at best, and patients afflicted with this disorder generally live with chronic pain, in and out of hospitals, throughout their lives. The disease bears the name of the investigator who convincingly distinguished this disease from intestinal tuberculosis in 1932. This distinction was not universally accepted, and the notion of a mycobacterial etiology has never been fully dismissed. Nevertheless, it was 46 years after the distinction of Crohn's disease and intestinal tuberculosis before research attempting to reassociate mycobacteria and Crohn's disease was published. Recently, there has been a surge of interest in the possible association of mycobacteria and Crohn's disease due largely to the isolation of genetically identical pathogenic Mycobacterium paratuberculosis from several patients with Crohn's disease in the United States, the Netherlands, Australia, and France. These pathogenic organisms have been isolated from only a few patients, and direct evidence for their involvement in the disease process is not clear; however, M. paratuberculosis is an obligate intracellular organism and strict pathogen, which strongly suggests some etiologic role. Immunologic evidence of a mycobacterial etiology, as assessed by humoral immune determinations, has been conflicting, but evaluation of the more relevant cellular immunity has not been performed. Data from histochemical searches for mycobacteria in Crohn's disease tissues have been equally conflicting, with acid-fast bacilli detected in 0 to 35% of patients. Animal model studies have demonstrated the pathogenic potential of isolates as well as elucidated the complexity of mycobacterial-intestinal interactions. Treatment of Crohn's disease patients with antimycobacterial agent has not been fully assessed, although case reports suggest efficacy. The similarities in the pathology, epidemiology, and chemotherapy of Crohn's disease and the mycobacterioses are discussed. The issue is fraught with controversy, and the data generated on the association of mycobacteria and Crohn's disease are in their infantile stages so that a general conclusion on the legitimacy of this association cannot be made. While no firm evidence clearly implicates mycobacteria as an etiologic agent of Crohn's disease, the notion is supported by suggestive and circumstantial evidence and a remarkable similarity of Crohn's disease to known mycobacterial diseases.

Mycobacterium avium subsp. paratuberculosis in powdered infant milk: paratuberculosis in cattle - the public health problem to be solved

“…The microbial sensing proteins involved in innate immunity recognise conserved and often structural components of microorganisms. Published data has strengthened the association of MAP with Crohn's disease already for two decades (Chiodini et al, 1984(Chiodini et al, , 1986(Chiodini et al, , 1989HermonTaylor et al, 2000;Autschbach et al, 2005;Sechi et al, 2005). Crohn's disease affects hundreds of thousands of people around the world.…”

“…The Colloquium also stated that it can be extremely difficult to prove that a pathogen is the cause of the chronic disorder when the onset of disease begins some time after the exposition. Often times it is not practical or even possible to use Koch's postulates to prove the infectious nature of chronic illnesses (Carbone et al, 2005) MAP and other agents (Clostridium spp., Campylobacter jejuni, Campylobacter feacalis, Listeria monocytogenes, Brucella abortus, Yersinia pseudotuberculosis, Yersinia enterocolica, Klebsiella spp., Chlamydia spp., Eubacterium spp., Peptostreptococcus spp., Bacteroides fragilis, Enterococcus feacalis, and Escherichia coli) are suspected to be possible triggers of Crohn's disease (Carbone et al, 2005), a chronic autoimmune inflammatory bowel disease with similar pathological changes to paratuberculosis (Chiodini, 1989). MAP cells contain peptidoglycans and heat shock proteins, which are able to initiate the inflammatory changes in the intestine (Elzaatari et al, 1995;Chamaillard et al, 2003).…”

The Role of Bacterial Infection in the Pathogenesis of Inflammatory Bowel Disease

“…Oral inoculation of one of the strains into a newborn goat produced a granulomatous ileocolitis after 5 months, and the authors concluded that the isolates were strains of M. paratuberculosis or a biovariant that plays an etiologic role in some cases of CD. Interestingly, M. paratuberculosis causes Johne's disease, an intestinal disorder in ruminants such as cattle, horse and goat that resembles CD both clinically and histologically (34). Other studies reported increased titers of antibodies to M. paratuberculosis antigens in CD patients (35)(36)(37).…”

Characterization of IS900 loci in Mycobacterium avium subsp. paratuberculosis and development of multiplex PCR typing The GenBank accession numbers for the sequences reported in this paper are AJ011838, AJ250015–AJ250023 and AJ251434–AJ251437.

“…M. avium subsp. paratuberculosis, which is very closely related to other M. avium subspecies, is a specific pathogen able to cause chronic inflammation of the intestine in ruminants, monogastrics such as dogs and pigs, and in subhuman primates (Larsen et al, 1971 ;McClure et al, 1987 ;Chiodini, 1989 ;Cocito et al, 1994). Our understanding of the genetic basis for this pathogenicity in M. avium subsp.…”