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Title: TRICHURIS SUIS GUT THERAPY IN CROHN'S DISEASE

Author
item SUMMERS, ROBERT - UNIV OF IOWA
item ELLIOTT, DAVID - UNIV OF IOWA
item Urban, Joseph
item THOMPSON, ROBIN - UNIV OF IOWA
item WEINSTOCK, JOEL - UNIV OF IOWA

Submitted to: Gut
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/15/2004
Publication Date: 1/1/2005
Citation: Summers, R., Elliott, D., Urban Jr, J.F., Thompson, R., Weinstock, J. 2005. Trichuris suis gut therapy in crohn's disease. Gut. 54:87-90.

Interpretive Summary: Mouse models of inflammatory bowel disease (IBD) have shown that infection with worms can prevent or ameliorate colitis. These experimental models were designed to test the hypothesis that humans from industrialized Western countries with few worm infections express immune dysregulation that results in increased expression of IBD compared to lesser developed countries where worm infections are common and IBD is infrequent. Pigs and man are co-infected with similar organisms because of comparable immune and physiological systems and agricultural practices that increase exposure. Trichuris species are whipworms that infect many different mammals but are host specific in their development to a complete infection. Man has been reported to be infected with the pig whipworm, but it does not develop into adult worms that shed eggs. The pig whipworm, Trichuris suis, appears to be asymptomatic in man and represents a naturally attenuated infection that cannot reproduce. This provided an opportunity to test the hypothesis that exposure to a worm would reduce the severity of IBD. A double-blind and placebo-controlled study was conducted at the University of Iowa. There was a significant improvement in Crohn's disease activity index (CDAI), in individuals that were refractory to other conventional forms of treatment, when they were fed T. suis eggs. This observation supports the hypothesis that immunological dysfunction may result from insufficient exposure to certain organisms that activate a balanced immune system. These results can be expected to impact the study of several other immunologically based diseases and the search for natural products that can substitute for worms and induce a protective response against IBD.

Technical Abstract: Crohn's disease is common where helminths are rare, and uncommon where most people carry worms. Helminths diminish immune responsiveness and reduce inflammation in experimental colitis. Twenty-nine patients ingested 2500 live Trichuris suis ova every three weeks for 24 weeks, and disease activity was monitored by Crohn's disease activity index (CDAI). At week 24, 23 patients (79'3%) responded (decrease in CDAI >100 points or CDAI <150), and 21/29 (72'4%) remitted (CDAI <150). The mean CDAI of responders decreased 177'1 points below baseline. There were no adverse events. This new therapy may offer a safe, efficacious alternative to immunosuppression in Crohn's disease.