MAP Research

Johne's Disease Connection
The microorganism, mycobacterium avium subspecies paratuberculosis, has been established in the veterinary literature to be the cause for Johne's disease, a disease causing colitis in cattle, sheep, and subhuman primate species.  This disease resembles, clinically, Crohn’s disease in humans and acts very much the same.   Studies in England and in Wales have shown the presence of mycobacterium paratuberculosis in milk and water supplies.  It is known that infected cows secrete this bacteria in milk and hence, milk borne infection appears to be theoretically possible. 

Crohn's Recognized
Crohn's disease was first recognized by a Glasgow surgeon, named Dalziel in 1913, when he first recognized that this disease was different than intestinal tuberculosis; however, similar to paratuberculosis in cows. At that time, he postulated a possible mycobacterial cause; however, failed to prove this connection, in that this organism could not be demonstrated microscopically or cultured. In 1932, Dr. Crohn and Dr. Ginzberg felt that this disease was not due to a mycobacterial origin since these Crohn’s patients were not found to have this bacteria visible microscopically and by culture technique. An important milestone in the research of mycobacterium occurred in 1985, when a genetic code (the IS900 insertion sequence) that is unique for mycobacterium paratuberculosis was found in both the bacillary and spheroplast forms of this microorganism.  A technique known as polymerase chain reaction (PCR technique) makes it possible to detect minute numbers of this mycobacterium paratuberculosis against other DNA signals present in the human body.  This sequence is very specific for this species of mycobacterium since there are many other known species that can cause disease (tuberculosis, avium, intracellulare, etc.). A number of studies have now confirmed the identification of mycobacterium in serum responses (antibody response), as well as in tissue studies (PCR studies), confirming the presence of this bacteria in patients with Crohn’s disease as compared with non-inflammatory bowel disease patients. The studies to date have shown this microorganism to be present in higher numbers percentage-wise in Crohn’s disease patients. 

Associated with CD
Consequently, the paratuberculosis problem not only includes the challenge of linking this bacteria to a specific disease, but also, the possibility that this mycobacterium paratuberculosis has been carried to human populations in certain foods and, in some areas, via the water supply. Most of us have been exposed to these bacteria and because of our immune systems ability to fight this bacteria, a transient intestinal infection will occur (short-lived diarrhea) and there will be no after effects. However, in those people genetically susceptible to inflammatory bowel disease (patients with a genetic predisposition, i.e. family history, or other risk factors such as immunosuppressed states), this infection can cause a disease, causing inflammation of the bowel and subsequent immune response, which is characteristic in patients with Crohn’s disease. The factors making one predisposed to this microorganism are, to date, undefined and recent genetic studies suggest a defect in chromosome 12 or chromosome 16 in patients susceptible to Crohn’s disease. Because of this association of mycobacterium paratuberculosis and the response to its pathogenicity, recurrent spells of exacerbation and remission, so characteristic of this disease, can occur. It is felt that in the early phase of this disease, clinical improvement can be achieved by killing the bacterium. There has been one clinical trial of patients with Crohn’s disease treated with a combined antibiotic therapy consisting of two antibiotics showing a 93.5 percent response rate in Crohn’s disease patients treated with a two-drug, long-term antibiotic therapy directed at mycobacterium paratuberculosis.  These patients showed a substantial improvement in symptoms and “remission of their disease” with no other therapy.  It appears that a small proportion of patients with Crohn’s disease required long term therapy to “maintain” their diseases.  Most achieve remission on several months of treatment. 

Investigations
It is hoped that the future investigation will search for mycobacterium paratuberculosis in Crohn’s patients by newer technologies, as we have relied heretofore on genetic probes (PCR), culture techniques (often times negative), or older antibody testing. Newer techniques will involve looking within tissue specimens of patients with Crohn’s disease for the spheroplast, which is the cell wall-less form of this bacteria, and a special technique using gold tagging which will ultimately allow for the identification of this particular bacterium in patients with Crohn’s to be compared with controlled populations of non-inflammatory bowel disease patients Ultimately, the identification of this bacteria by multiple modalities will prove the association and lead to further trials of treatment of Crohn’s disease patients with antibiotics.  Since mycobacterium paratuberculosis is often resistant to conventional antibiotics, newer forms of treatment will need to be studied to pursue more effective treatments.  It is hoped that natural compounds from plants will prove to be effective and nontoxic in eradicating this bacteria.  The combined ability to detect this bacteria by a non-invasive and sensitive and specific technique in the genetically predisposed patients will allow for eradication of the bacteria at an early stage and ultimately prevention of the disease known as Crohn’s disease. 

Ultimately, Crohn’s disease, which in the United States costs between 1 and 1.2 billion dollars per year, will someday not only be treatable, but preventable. 
 

The information contained in this site is intended for information purposes only and is not intended as a means of diagnosing or treating disease. Please consult your doctor before starting any treatment.