How parasitic worms cure inflammatory bowel disease

Whipworm Inflammatory bowel disease sufferers (IBD, including Crohn’s disease and ulcerative colitis) experience a variety of unpleasant symptoms such as abdominal pain, vomiting, diarrhoea, rectal bleeding, severe internal cramps/muscle spasms in the region of the pelvis and weight loss. The causes of these diseases are complex and not well understood, but the incidence of IBD is highest in industrialized regions where helminth (parasitic worm) infections have been largely eliminated. This raises the possibility that helminth infections may protect against intestinal inflammation underlying the disease (Inflammatory bowel disease: cause and immunobiology. (2007) The Lancet, 369 (9573), 1627-1640). But no-one wants to be infected with parasitic worms – do they?

IBD is so unpleasant that a number of clincial trials involving deliberate infection of informed volunteers with Trichuris suis have been carried out – with some success (Helminths as governors of inflammatory bowel disease. (2008) Gut, 57(8), 1182-1183). Exactly how the worms help to quell the inflammatory symptoms remained to be completely explained.

Monkeys kept in captivity at Primate Research Centers often develop chronic diarrhoea and bowel disease which shares many features with ulcerative colitis. A new paper tested treatment of captive macaques suffering from this condition with human whipworms. Four out of five treated macaques showed reduced symptoms. After treatment with worms, the monkeys had less bacteria attached to their intestinal wall and a reduced inflammatory response to the gut bacteria. Also, the composition of gut bacteria which was altered in the sick macaques was restored close to the normal flora after treatment with whipworms. These results provide a potential mechanism by which parasitic worms may improve the symptoms of intestinal inflammation, by reducing the immune response against intestinal bacteria.

Immunologic mechanisms underlying the amelioration of colitis

Therapeutic Helminth Infection of Macaques with Idiopathic Chronic Diarrhea Alters the Inflammatory Signature and Mucosal Microbiota of the Colon. (2012) PLoS Pathog 8(11): e1003000. doi:10.1371/journal.ppat.1003000
Young macaques kept in captivity at Primate Research Centers often develop chronic diarrhea, which is difficult to treat because it is poorly understood. This disease shares many features with ulcerative colitis, which is an autoimmune disease affecting the intestinal tract of humans. Recently, parasitic worms have been used in clinical trials to treat inflammatory bowel diseases in humans with positive results, but very little is known about how worms can improve symptoms. We performed a trial where we treated macaques suffering from chronic diarrhea with human whipworms, collecting gut biopsies before and after treatment. We found that 4 out of the 5 treated macaques improved their symptoms and studied the changes in their gut immune responses, as they got better. We found that after treatment with worms, the monkeys had less bacteria attached to their intestinal wall and a reduced inflammatory response to the gut bacteria. Additionally, the composition of gut bacteria was altered in the sick macaques and was restored close to normal after treatment with whipworms. These results provide a potential mechanism by which parasitic worms may improve the symptoms of intestinal inflammation, by reducing the immune response against intestinal bacteria.

 

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