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Gut 49:757-760 doi:10.1136/gut.49.6.757
  • Debate
  • ANTAGONIST

Mycobacterium avium subspecies paratuberculosis is a cause of Crohn's disease

  1. P Quirke
  1. Academic Unit of Pathology, University of Leeds, Leeds LS2 9JT, UK
  1. Professor P Quirke.philq{at}pathology.leeds.ac.uk
  • Accepted 5 September 2001

The hypothesis that Mycobacterium paratuberculosis is the cause of Crohn's disease has been with us for over 80 years.1 Yet the hypothesis remains controversial and unproved.2-5 In spite of advances in molecular techniques such as polymerase chain reaction (PCR) which has shed light on the infectious basis of many other diseases (Whipple's disease, Helicobacter pylori, hepatitis C, etc.), the cause of Crohn's disease remains unknown.

The competing hypotheses are widely known:

(1)
Genetic predisposition.
(2)
Other infectious agents such as measles virus or an unknown agent.
(3)
Abnormal autoimmune reaction to antigen(s).
(4)
Environmental factors within the gut related either to dietary factors or the microbiological environment.

 There is little controversy over a genetic component to the disease but this hypothesis alone cannot explain the increasing incidence. It appears most likely that the cause of Crohn's disease is a combination of a genetic predisposition to the disease and one or more of the alternative hypotheses. For the infectious disease hypothesis to be proved for any organism, Koch's postulates need to be fulfilled. It is clear that to date these have yet to be met forM paratuberculosis. Van Kruiningen2 has extensively reviewed the data on culture of M paratuberculosis in Crohn's disease, experimental transmission of Crohn's disease, and inoculation withM paratuberculosis, and has found the evidence wanting. There is also no evidence of direct transmission from animal to humans, despite the frequent occurrence ofM paratuberculosis (up to 54% in some cattle herds3) and Johne's disease in cattle, its detection in cows milk, and the presence of M paratuberculosis in a number of other animals. High risk groups susceptible to transmission of the disease would be families of cattle and sheep farmers, abattoir workers, veterinary surgeons, and possibly gastroenterologists. To date, there is no such evidence.

There are pathological similarities between Johne's disease and Crohn's disease but there are also many features that are not found. These are eloquently detailed by Van Kruiningen2 and will not be …