Sept. 16, 2004 -- A treatable infection may be the cause of Crohn's
disease, new evidence shows.

The idea that a germ causes Crohn's disease isn't new. It goes back
to 1913, when a surgeon noticed that the ulcer-ridden intestines of
people with Crohn's disease look a lot like the intestines of
animals with Johne's disease.

Scientists later learned a relative of the tuberculosis germ,
Mycobacterium avium paratuberculosis, or MAP, causes Johne's
disease. Does MAP cause Crohn's disease, too? That has been hard to
prove. Why? MAP is incredibly hard to grow in the lab. It has been
hard to show that Crohn's patients carry the living bug -- the first
step in proving that MAP is the Crohn's culprit.



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That has changed. Saleh A Naser, PhD, associate professor of
molecular biology and microbiology at the University of Central
Florida, Orlando, developed a better way to culture MAP. Now he
reports that he can grow living MAP from the blood of 50% of
patients with Crohn's disease, 22% of people with ulcerative
colitis -- and none from patients who don't have inflammatory bowel
disease.

"We have strong evidence now that MAP is responsible for many cases
of Crohn's disease -- maybe two-thirds of cases, we do not yet
know," Naser tells WebMD. "We should be concerned that these
bacteria are present in patients with Crohn's disease."

Naser and colleagues report their findings in the Sept. 18 issue of
The Lancet.

The Proof in the Pudding -- Treatment

Simply showing that Crohn's patients are more likely to have MAP
infection than healthy people doesn't prove MAP causes the illness,
warns Warwick Selby, MD, clinical associate professor of
gastroenterology at the University of Sydney in Australia.

"The Naser findings are interesting and provocative," Selby tells
WebMD in an email interview. "However, as with all of the studies
looking at MAP in Crohn's disease, it does not prove that MAP is the
cause."

Selby's editorial appears alongside the Naser team's report in The
Lancet.

MAP "does seem to be there," Selby says. But that might only mean
that existing Crohn's disease damages the intestinal wall, and lets
MAP and other bacteria out of the gut and into the bloodstream.

What would prove a connection? Selby would be convinced if Crohn's
patients get better after taking MAP-killing drugs. Even though he's
been skeptical about the MAP-Crohn's connection, he's leading a
study in which 214 patients received two years of a potent anti-MAP
drug combination.

"The Australian trial was specifically designed to use antibiotics
that would be effective against MAP," Selby says. "We used
clarithromycin [Biaxin], rifabutin [Mycobutin], and clofazimine
[Lamprene] for two years. All patients were initially treated with a
course of [steroids] for 16 weeks as well and were randomized to
antibiotics or placebo. After their two-year course of treatment
they were then followed for one year off trial therapy."

The trial is finished and the data should soon be available.

"Until the results of the trial are available, the benefit of this
is unproven," Selby warns. "Anecdotal reports have indicated some
patients respond but this may be the case with other antibiotic
regimes as well. Standard antimycobacterial therapy, such as what
would be used for tuberculosis, is not effective in Crohn's disease.
I would not recommend widespread use of anti-MAP therapy until we
know what the trial showed."

But Naser disagrees. He says the standard treatment for Crohn's
disease -- anti-inflammatory steroids that reduce intestinal
swelling and normalize intestinal function -- can give only short-
term relief.

"If you have Crohn's disease, or ulcerative colitis, or irritable
bowel syndrome, do not settle for anti-inflammatory medications," he
says. "Get tested for MAP. There are antibiotics proven to be
effective. So get diagnosed, get tested, and get the right
treatment. Do not settle for steroids."

MAP in Milk?

If MAP does turn out to cause Crohn's disease, it could be a major
public health problem. That's because live MAP has been found in
pasteurized milk.

"There is only one source of MAP -- contaminated water, milk, or
beef. It is not present in the environment," Naser says. He notes
that British researchers found the bacteria in pasteurized milk in a
supermarket in Wales. "This bacterium is tougher than we think. It
is resistant to pasteurization."

Women with Crohn's disease might pass the bug to their children.
Naser has isolated MAP from the breast milk of women with Crohn's
disease.

So why don't we all have Crohn's disease? Naser says that not
everybody has been exposed to the bug. And most people, he suggests,
don't easily get MAP infection. Naser suggests that some people have
a specific genetic flaw that allows MAP to gain a foothold in the
gut.


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SOURCES: Naser, S.A. The Lancet, Sept. 18, 2004; vol 364: pp 1039-
1044. Selby, W. The Lancet, Sept. 18, 2004; vol 364: pp 1013-1014.
Saleh A Naser, PhD, associate professor of molecular biology and
microbiology, University of Central Florida, Orlando. Warwick Selby,
MD, clinical associate professor of gastroenterology, University of
Sydney, Australia.