New hints on how helminth worms heal ulcerative colitis
A 34-year-old Northern California man with ulcerative colitis who decided to treat himself by swallowing parasitic worms has provided new information about how the worms might help to soothe and heal a variety of intestinal inflammations, researchers reported Wednesday. A growing body of evidence suggests that several different types of parasitic worms might be useful in treating such disorders, but there has been little evidence about how the worms might bring about positive changes. By allowing doctors to monitor changes in his immune system following ingestion of the worms, the man has provided the first clues about that mechanism.
For several decades, researchers have argued that the growing incidence of autoimmune disease in the developed world is the result of improved sanitation, which limits our exposure to infectious diseases during childhood. That exposure, some argue, trains the immune system not to overreact to a variety of germs encountered later in life. In its absence, exposure provokes autoimmune reactions. In the 1990s, Dr. Joel Weinstock, then at the University of Iowa and now at Tufts University, observed that the eradication of intestinal worms in the developed world was followed soon after by a rise in inflammatory bowel disease, which now affects as many as 1 million Americans. Inflammatory bowel disease is a general term that includes Crohn’s disease, which occurs in the large and small intestines, and ulcerative colitis, which is restricted to the colon. Ulcerative colitis affects only the innermost lining of the colon, causing severe lesions, while Crohn’s affects all three layers. Each affects about 500,000 Americans. Symptoms for both include diarrhea, crampy abdominal pain and rectal bleeding.
After tests in mice, Weinstock and his colleagues had four patients with Crohn’s and two with ulcerative colitis drink a solution containing eggs of the pig whipworm (Trichuris suis), which frequently infects pig farmers but normally does not cause illness in humans. Five of the subjects went into remission and the sixth improved substantially.
In 2005, Weinstock published results from two clinical trials. In one, 23 of 29 Crohn’s patients responded positively to the worms (which die off in the body after four to five weeks) and 21 went into complete remission. In the second, 13 of 30 ulcerative colitis patients improved after receiving the eggs.
P’ng Loke, a parasitologist at New York University Medical Center, was a post-doctoral fellow at UC San Francisco in 2006 when he received a call from a young man who was looking for someone knowledgeable about helminth (worm) immunology. Loke agreed to meet him for lunch and hear his story. The man suffered from severe ulcerative colitis and had no longer been responding to steroids. He had been on a path toward even more potent immunosuppressive drugs and, most likely, removal of his colon, Loke said -- which is the fate of many colitis patients. “A very intelligent and impressive young man who had done a lot of research,” he had contacted a parasitologist from Thailand and obtained a sample of the parastic worm Trichuris trichiura. Unlike T. suis, which is eliminated from the body in a few weeks, T. trichiura establishes a much longer lasting infection. When Loke met him, his colitis was in remission. He was curious not only how that had been accomplished but also what could be done if he had a relapse.
Loke and his colleagues obtained histology slides taken before the man consumed the worms and compared them with his new situation. They reported in the journal Science Translational Medicine that, when he had active disease, he had large numbers of CD4 immune cells that produced an inflammatory protein called interleukin-17. After he had consumed the worms, however, the number of those cells decreased and he had larger numbers of cells that produced interleukin-22, a protein that is important in healing the intestinal mucosa. “In essence, the worms trigger a big sneeze of the gut, which may have a beneficial side effect for ulcerative colitis,” he said.
Loke does not advocate using T. trichiura for treating colitis. For one thing, it can cause intestinal damage itself, and the young man was lucky that it did not. For another, there is no good source of medical grade parasite available in this country, he said, and it is unlikely that either the Food and Drug Administration or a university ethical committee would approve any kind of trial. For the time being, he said, his team will continue working with T. suis.
