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Thursday, November 29, 2012

The whipworm treatment for inflammatory bowel disease



Some parts of the world have high incidences of inflammatory bowel disease (IBD). Those regions tend to have at least one factor in common: low rates of intestinal worm infection. Doctors have been investigating this intriguing connection and finding that giving people worms can actually benefit them. For example, people with ulcerative colitis (a type of IBD) have been helped by worm treatment.  But why is this so? Researchers, led by Mara Jana Broadhurst of the University of California, San Francisco and P’ng Loke of New York University, suggest that patients suffering from IBD have compromised mucosal barriers in their intestines, and that this defect is remedied by worm infestation.

A good model for ulcerative colitis is the idiopathic chronic diarrhea often suffered by captive baby rhesus macaque monkeys. The scientists treated five baby monkeys who had this illness by infecting them with the whipworm Trichuris trichiura. The researchers performed colonoscopies on the monkeys just prior to treatment and fourteen weeks after the worm treatment.

Four of the monkeys improved after the worm treatment, as shown both by weight gain and stool consistency. In addition, the colon biopsies revealed that the monkeys had a decreased inflammatory response after being infected with the worms. The mucosal layer of the primates’ intestines was restored to almost normal. Perhaps most significantly, the monkeys’ mucosal bacterial communities were also restored.

The authors summarize their hypothesis below:

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Working model of the immunologic mechanisms underlying the amelioration of colitis in the setting of Trichuris sp. treatment.
(A)  Colitis is driven by a TH1-type inflammatory response to increased bacterial attachment and dysbiosis at the mucosal epithelium as a result of compromised barrier function.
(B)  Trichuris sp. elicits a mucosal TH2-type response (including the canonical cytokines IL-4 and IL-13) that promotes mucosal wound healing and mucus production. These functions reduce bacterial attachment and restore microbial homeostasis, removing the inflammatory stimulus.

Two things about this study. First, the authors did not include any controls. That is, all five of the monkeys received the worm treatment, none were untreated or received placebo. The researchers claim that there is plenty of evidence for how untreated baby monkeys fare under similar conditions. That may be true but further experiments including controls must be conducted before any broad conclusions are reached, something the authors agree to. Second, how glad are you that it isn’t your job to catalog monkey feces for consistency and quantity?

Mara Jana Broadhurst, Amir Ardeshir, Bittoo Kanwar, Julie Mirpuri, & et al. (2012). Therapeutic Helminth Infection of Macaques with Idiopathic Chronic Diarrhea Alters the Inflammatory Signature and Mucosal Microbiota of the Colon PloS ONE Pathogens : doi:10.1371/journal.ppat.1003000