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Pathogens & People: Agony and mystery of Crohn's Disease

By EDWARD McSWEEGAN, For The Capital

Published January 04, 2009

About 75 years ago, an American physician described a gastrointestinal disorder that was similar
to intestinal tuberculosis. Today, that disorder is known as Crohn's disease. Unfortunately, after
75 years, there are still many unanswered questions about this disease, including the cause. There
also is no cure and no truly effective therapy.

What Dr. Burrill Crohn described in 1932 is a chronic inflammation of the intestinal tract.
Common symptoms include abdominal pain, persistent diarrhea, weight loss and malnutrition,
and occasional bleeding and anemia. It is a painful, unpredictable condition that can make
normal work schedules and social activities difficult. The Centers for Disease Control and
Prevention estimates there may be 500,000 people in the United States with Crohn's disease.
What causes it? It was thought to be an immune disorder, so steroids and other anti-inflammation
and immunosuppressive agents have been prescribed, along with anti-diarrheal drugs. In severe
cases, surgeons can remove ulcerated or infected parts of the affected intestine.

Interestingly, humans are not the only species to suffer from such a depressing and disastrous
disorder. Cattle also suffer from a Crohn's-like illness called Johne's disease. This bovine illness
is an infection caused by Mycobacterium avium paratuberculosis, a bacterial cousin of the
tuberculosis bug.

Could the MAP bacteria also cause Crohn's disease in people? It's a good bet, but showing
causality is proving to be difficult. Still, if you can identify a cause, you can design a cure, and
MAP seems like a good place to start.

How would a person acquire bacteria that are normally associated with a livestock infection? Not
many people spend time around cattle herds, but it is possible the MAP bacteria may be
transmitted through contaminated meat and dairy products. MAP frequently survives standard
milk pasteurization, for example. Alternatively, it could be transmitted through soil and water
contaminated by livestock waste.

The majority of patients with Crohn's disease usually test positive for the presence of MAP. Yet,
ranchers and dairy farmers - who might be expected to have greater exposure to MAP - do not
have higher rates of Crohn's disease. So perhaps there is also a degree of genetic susceptibility in
some people that allows MAP exposure to progress to active infection and overt disease.

If Crohn's is caused by MAP bacteria it should be treatable with antibiotics. Indeed, some
Crohn's disease patients readily respond to antibiotic treatments. For those who do not respond, it
may be a matter of finding the most effective combination of antibiotics and the most effective
length of treatment time. So far, it's been mostly guesswork. Common anti-TB drugs were used
until it was discovered that MAP is resistant to them. Since then, a cocktail of three antibiotics -
rifabutin, clarithro-mycin and clofazimine - have been used to treat patients in the U.S. and
Australia.

A two-year study of 213 Crohn's disease patients in Australia ended in 2007. The study used the
three antibiotics listed above, but the results only seemed to add to the confusion and controversy
about MAP as a definitive cause of Crohn's. In medical journals, the study was called "flawed"
because the researchers apparently used suboptimal antibiotic doses and failed to detect MAP in
patients before or after treatment. To be fair, the gastrointestinal tract is a hostile environment to
researchers trying to study drug effects on a single type of bacteria. The human intestinal tract
contains numerous chemical and physical barriers; has a rapid turnover of cells and actively
empties the intestinal contents; contains acids, bile and digestive enzymes; and is home to
trillions of other bacteria that normally live there. MAP is a very small target in a very crowded,
chaotic environment.

Still, research and treatment trials continue. Earlier this year, the American Academy of
Microbiology released a report on expert recommendations for more research on MAP and
Crohn's disease. The report laid out a compelling case for MAP's involvement in Crohn's disease,
and recommended more laboratory research on diagnosing MAP and measuring the bacteria's
susceptibility to various antibiotics. Two other important questions that need answers are: how is
the disease transmitted and who is susceptible to MAP and subsequent disease? Commenting on
the report, study director Carol Nacy of Sequella Inc. in Rockville said, "We still have a long
way to go."

For more information about Crohn's disease, see the Crohn's and Colitis Foundation of America
at www.ccfa.org.
For ongoing treatment trials for Crohn's patients, search www.clinicaltrials.gov.

Dr. Edward McSweegan has a Ph.D. in microbiology and lives in Crofton. He works on and
writes about infectious disease issues. He may be contacted at mcsweegan@nasw.org.