Mycobacterium paratuberculosis as a cause of Crohn’s disease

Abstract

Crohn’s disease is a chronic inflammatory bowel disease of unknown cause, affecting approximately 1.4 million North American people. Due to the similarities between Crohn’s disease and Johne’s disease, a chronic enteritis in ruminant animals caused by Mycobacterium avium paratuberculosis (MAP) infection, MAP has long been considered to be a potential cause of Crohn’s disease. MAP is an obligate intracellular pathogen that cannot replicate outside of animal hosts. MAP is widespread in dairy cattle and because of environmental contamination and resistance to pasteurization and chlorination, humans are frequently exposed through contamination of food and water. MAP can be cultured from the peripheral mononuclear cells from 50–100% of patients with Crohn’s disease, and less frequently from healthy individuals. Association does not prove causation. We discuss the current data regarding MAP as a potential cause of Crohn’s disease and outline what data will be required to firmly prove or disprove the hypothesis.

Keywords:

• Crohn’s disease
• Helicobacter pylori
• Inflammatory bowel disease
• Johne’s disease
• Mycobacterium avium subspecies paratuberculosis
• prevention
• treatment trials

Financial & competing interests disclosure

DY Graham is supported in part by the Office of Research and Development Medical Research Service Department of Veterans Affairs, Public Health Service grant DK56338 which funds the Texas Medical Center Digestive Diseases Center. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the VA or NIH. DY Graham is a paid consultant for Red Hill Biopharma regarding novel H. pylori therapies and is the Principal Investigator for the ongoing Red Hill clinical trial entitled A Phase III Randomized, Double Blind, Placebo-controlled, Multicenter, Parallel Group Study to Assess the Efficacy and Safety of Fixed-dose Combination RHB-104 in Subjects with Moderately to Severely Active Crohn’s Disease. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Mycobacterium avium subspecies paratuberculosis (MAP) is a ubiquitous pathogen that cannot replicate in the environment and is widely present in food and water sources of humans.

• MAP causes Johne’s disease, a chronic enteritis, in cattle and other ruminant animals.

• Accumulating evidence supports a causative association between MAP and Crohn’s disease in humans.

• Viable MAP and its DNA can be detected in high percentages of blood and tissue from Crohn’s disease patients.

• Crohn’s disease may occur in clusters or epidemics in which MAP is detected in the environment.

• Genes associated with susceptibility to Crohn’s disease and MAP infection overlap significantly.

• MAP-specific treatments appear to promote the resolution of symptoms and healing of mucosal damage. Placebo-controlled trials are needed to confirm the specificity of these findings.

• Proof that MAP causes Crohn’s disease will result in a major change in the cattle and dairy industries similar to those that occurred during the program to eliminate bovine tuberculosis.

Notes