University of Wisconsin–Madison

Can MAP cause Crohn’s disease?

Medical gastroenterologists commonly raise five concerns that seem to argue against a role for MAP in Crohn’s disease.

They are:

  1. Why is there variability in studies which aim to detect MAP in Crohn’s patients?
  2. Has MAP fulfilled Koch’s postulates?
  3. Why does immunosuppressive therapy not worsen Crohn’s Disease if it is caused by MAP, as is seen with MTB (the cause of tuberculosis)?
  4. Why is the incidence of Crohn’s not higher in at‑risk subgroups, such as veterinarians or farmers?
  5. If MAP causes Crohn’s, why doesn’t atypical mycobacterial antibiotic therapy (AMAT) cure Crohn’s, and related to that, have RCTs (randomized controlled clinical trials) shown that AMAT is ineffective?

Dr. Gurav Agrawal and colleagues (myself included) published and invited review in the journal Digestive Diseases and Sciences addressing these 5 questions. The article is Open Access (11 pages with 86 references).

Abstract

For decades, Mycobacterium avium subspecies paratuberculosis (MAP) has been linked to the pathogenesis of Crohn’s disease. Despite many investigations and research efforts, there remains no clear unifying explanation of its pathogenicity to humans. Proponents argue Crohn’s disease shares many identical features with a granulomatous infection in ruminants termed Johne’s disease and similarities with ileocecal tuberculosis. Both are caused by species within the Mycobacterium genus. Sceptics assert that since MAP is found in individuals diagnosed with Crohn’s disease as well as in healthy population controls, any association with CD is coincidental. This view is supported by the uncertain response of patients to antimicrobial therapy. This report aims to address the controversial aspects of this proposition with information and knowledge gathered from several disciplines, including microbiology and veterinary medicine. The authors hope that this discussion will stimulate further research aimed at confirming or refuting the contribution of MAP to the pathogenesis of Crohn’s disease and ultimately lead to advanced targeted clinical therapies.

Worth noting:

As evidence that some gastroenterologists think MAP is a cause of Crohn’s disease, in the UK, a phase I clinical trial has started to investigate the safety and efficacy of two candidate MAP vaccines in patients with active Crohn’s disease (ISRCTN – ISRCTN36126048).