Tractable Preclinical Model Proposed for Ulcerative Colitis
Helminth therapy thought to restore mucosal barrier functions, reduce bacterial attachment
MONDAY, Nov. 19 (HealthDay News) -- A parasitic worm can improve chronic diarrhea in monkeys by altering the immune response and bacterial species present in the intestine, providing a possible preclinical model for the treatment of ulcerative colitis, according to research published online Nov. 15 in PLOS Pathogens.
Mara Jana Broadhurst, Ph.D., from the University of California San Francisco, and colleagues exposed five rhesus monkeys with idiopathic chronic diarrhea to the whipworm Trichuris trichiura.
The researchers found that four monkeys had improved fecal consistency and weight gain after treatment. Biopsies of intestinal mucosa showed a reduction in TH1-type inflammatory gene expression and induction of the mucosal TH2 response, which was associated with a reduction in CD4+ Ki67+ cells. In addition, expression of genes linked to immunoglobulin E signaling, mast cell activation, eosinophil recruitment, alternative activation of macrophages, and worm expulsion was increased. There was reduced bacterial attachment to the intestinal mucosa and changes in the composition of microbial communities attached to the intestinal mucosa. Before treatment, cyanobacteria genus Streptophyta was increased in abundance in three of the monkeys and was reduced after treatment, while the phylum Tenericutes was increased post-treatment.
"These findings suggest that helminth treatment in primates can ameliorate colitis by restoring mucosal barrier functions and reducing overall bacterial attachment, and also by altering the communities of attached bacteria," Broadhurst and colleagues conclude. "These results also define idiopathic chronic diarrhea in monkeys as a tractable preclinical model for ulcerative colitis in which these effects can be further investigated."