Is there evidence for a link between Crohn's disease and exposure to Mycobacterium avium ssp. paratuberculosis? A review of current literature
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Series/Report no.
RIVM Rapport 230086001Type
ReportLanguage
en
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Is there evidence for a link between Crohn's disease and exposure to Mycobacterium avium ssp. paratuberculosis? A review of current literatureTranslated Title
Literatuuroverzicht van het bewijs voor een mogelijk verband tussen de ziekte van Crohn en blootstelling aan Mycobacterium avium ssp. ParatuberculosisPubliekssamenvatting
Mycobacterium avium ssp. paratuberculosis (Map) wordt door veel onderzoekers beschouwd als mogelijke verwekker van de ziekte van Crohn (morbus Crohn, MC) bij de mens. Dit is vooral gebaseerd op klinische en pathologische overeenkomsten tussen MC en de ziekte Paratuberculose bij runderen (herkauwers), die zonder twijfel veroorzaakt wordt door Map, en de aangetoonde aanwezigheid van Map bij een deel van de patienten met MC. Echter, evenzoveel onderzoekers zijn van mening dat Map niet de verwekker is van MC omdat Paratuberculose en MC ook verschillen in een aantal kenmerken. Map kan bijvoorbeeld niet worden aangetoond bij alle MC patienten. Verder kan Map vaak wel worden aangetoond bij een aanzienlijk deel van de onderzochte gezonde personen. Omdat Map niettemin een ziekteverwekker is die via melk, vlees, water en andere levensmiddelen de consument kan bereiken, bestaat er ernstige bezorgdheid over het mogelijke risico van dit Map-besmet voedsel voor het ontstaan van MC bij de consument. In dit rapport wordt een antwoord gegeven op de vraag 'is het verband tussen de verwekker van Paratuberculose, Mycobacterium avium ssp. paratuberculosis, en de ziekte van Crohn overtuigend bewezen?' De huidige wetenschappelijke kennis over MC wordt beschreven, waarbij het accent wordt gelegd op de informatie die direct of indirect betrekking heeft op, of een indicatie kan zijn voor een mogelijke relatie tussen MC en Map.Crohn's Disease is characterized by a severe, non-specific, chronic inflammation of the intestinal wall. The inflammation of CD most commonly affects the last part of the ileum, and often includes the colon and sigmoid. CD is a Th1 disease characterized by the production of pro-inflammatory cytokines like TNF- , which is responsible for development of the lesions, and by the production of IFN-? and Il-2. CD is a multi-factorial disease; based on epidemiological and geographical observations, several genetic (familial, racial) and environmental (geographic, hygienic) factors (especially microbial) have been associated with the disease. Mutations in the human CARD15 gene and differential expression of Toll-like receptors (TLRs) 2, 3 and 4 have been associated with CD. CARD15 and TLRs are part of the body's innate defence system against bacteria. They activate the immune system after recognizing specific bacterial components. Presence of intestinal bacteria seems to be a prerequisite for CD; the disease cannot develop or perpetuate without the presence of an intestinal flora. One of the bacteria that has been frequently associated with CD is Mycobacterium avium subspecies paratuberculosis (Map). Map causes a severe chronic intestinal disease in ruminants, Paratuberculosis. CD and Paratuberculosis share several clinical, immunological and histo-pathological characteristics. Map is present in many dairy herds and probably can be transmitted to humans via foodstuff. Many investigators have tried to prove, or controvert a common aetiology for CD and Paratuberculosis, and have applied several detection methods to accomplish this. Unfortunately, the quest for Map using PCR and culture methods, and the studies on the immune responses against Map in CD patients, have yet not resulted in conclusive data to support or discount the hypothesis that Map is the etiologic agent of CD. The fact that Map can be found in a high percentage of apparently healthy individuals, and that CD patients have significantly higher immune responses against several food antigens compared to healthy individuals, raises the question whether Map is a common passer-by of the human intestinal tract, or that a particular cofactor (a genetic aberration) is needed before Map can cause disease. The current hypothesis about the patho-physiology of CD is that in a genetic susceptible host, the intestinal flora triggers an aberrant immune response that results in a chronic intestinal inflammation and a damaged (leaky) intestinal mucosal barrier. Although a multi-factorial cause for CD is expected, the possibility, however, that an infectious agent like Map can play a key role in the causation of even a sub-set of CD patients remains, and clearly needs to be taken seriously.
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