Antibiotics for Crohn's Disease

Sophisticated laboratory techniques are helping confirm the link between Crohn's disease and the Mycobacterium avium subspecies paratuberculosis, or MAP bug, offering hope for a cure to thousands of people living with what has been considered an incurable condition. The hypothesis that bacteria may cause the painful and debilitating digestive disease was first suggested almost a century ago.

"The reason that it has taken so long for the issue to become clarified is because the Mycobacterium avium subspecies is extremely difficult to investigate in the laboratory," professor John Hermon-Taylor, St. George's Hospital Medical School, University of London, told MU. "It doesn't grow consistently in culture. Secondly, MAP can switch from a red-staining form to a very tough 'teflon-coated' invisible form which hides inside cells."

Dr. Hermon-Taylor and his team adapted a genetic testing method called polymerase chain reaction to look for the organism in tissue samples taken during an endoscopy.

"We found that you had to include a special step in processing the tissue sample in order to access MAP DNA reliably," he explained. "When we did this, we found that virtually everyone with Crohn's disease is infected with MAP."

The MAP bug is known to cause chronic intestinal inflammation in cows. In the early '90s, research showed there was a high risk that the MAP bug was being transmitted to humans in pasteurized cow's milk products.

A historical perspective is important when considering the risk of MAP infection, according to the London-based researcher.

"In the first half of the 20th century, most of the population of Western Europe and North America drank live, virulent tuberculosis bacilli before pasteurization of milk was generally implemented. Only a small percentage of the people exposed to the bacilli came down with TB. The same thing is happening with the MAP bug. You have either to inherit or acquire a susceptibility to be at risk of developing disease. Alternatively, you might get a huge dose of MAP just after having had the flu, or you may be exposed to a particularly nasty strain. We know that there are differences in the genomes and behavior of different human isolates of MAP.

"Milk would be a major route of transmission of Crohn's," he continued. "Another potential route is from the environment. There is a risk that MAP may be conveyed to human populations in contaminated rivers, lakes, and reservoirs. Water treatment procedures substantially deplete the MAP content, but they don't appear to eliminate the MAP bugs completely."

Ultrahigh temperature (UHT) pasteurization eliminates most contaminants, including the Mycobacterium avium subspecies paratuberculosis. UHT milk products are available on the Internet and in some health-food stores. Alternately, boiling milk products at home would almost certainly kill MAP bugs, advises Dr. Hermon-Taylor.

"If you feel yourself to be particularly at risk of Crohn's disease, you may decide to heat milk above 80 degrees Centigrade (177 to 185 degrees Fahrenheit), set it aside to cool, and then refrigerate in the usual way. It will deplete any residual live MAP and may eliminate them."

Dr. Hermon-Taylor and his team have discovered that a combination of certain antibiotics often eradicates MAP from the body.

"There are now four open-label clinical studies which essentially all say the same thing," said Dr. Hermon-Taylor. "That is, that somewhere between 50 to 75 percent of people with active Crohn's disease who can take rifabutin and clarithromycin treatment will get better and heal--sometimes like magic. The people who do not respond are infected with MAP which is already resistant."

Results of a recent randomized trial will better determine the role of the MAP bug in Crohn's disease. Currently, less than one percent of gastroenterologists are prescribing antibiotics for the disease.

"While the data are not yet publicly available, it is highly likely that the trial will confirm the consistent results of the open label studies. That is, that a substantial proportion of people sick with Crohn's disease will heal when treated with these agents," explained Dr. Hermon-Taylor.

"I have a cohort of people, some of them quite young, who had end-stage colonic Crohn's and were facing irreversible surgery and a lifetime of living with an abdominal stoma, who are today walking around living normal lives because of these anti-MAP drugs.

"One is a veterinarian in Germany. In November 2000 he developed a left-sided colitis involving the descending colon and rectum. He was diagnosed by his local gastroenterologist as having Crohn's disease and treated with the usual immunosuppressive agents. He got better, then worse, and was facing surgery when he came to London in July 2001. We did the MAP test, and it was strongly positive throughout the diseased area. He has been treated with rifabutin and clarithromycin. We have just re-endoscoped him, testing mucosal biopsies histologically and for MAP. He is completely healed, and the MAP test has become negative."

Crohn's disease attacks the small and large intestines. Characteristic symptoms include diarrhea, abdominal cramps, weight loss, and complications such as bowel obstruction and abscesses.

Last updated Jan 4/07