Probiotic Worm Treatment May Improve Symptoms of Colitis by Restoring Gut Bacteria to Healthy State
ScienceDaily (Nov. 15, 2012) — A new study on monkeys with chronic diarrhea that were treated by microscopic parasite worm (helminth) eggs has provided insights on how this form of therapy may heal the intestine. This condition in monkeys is similar to the inflammatory bowel diseases that affects up to 1.4 million Americans.
The study, published November 15 in the Open-Access journal PLOS Pathogens, shows that helminths can restore the balance of gut bacterial communities to the monkeys with chronic diarrhea.
Inflammatory bowel diseases are driven by a misdirected immune response against gut bacteria (the microbiome) and are often associated with alterations in gut bacterial communities (known as dysbiosis).
“The idea for treating colitis with worms is not new, but how this therapy might work remains unclear,” says the study’s senior corresponding author, P’ng Loke, PhD, assistant professor of microbiology at NYU Langone Medical Center. “Our findings suggest that exposure to helminths may improve symptoms by restoring the balance to the microbial communities that are attached to the intestinal wall.”
Because inflammatory bowel diseases are more common in countries with developed economies and is rare in developing countries, researchers have hypothesized that endemic helminth infections in developing countries may offer protection against this disease. In animal models of autoimmunity these worms have suppressed inflammation, and clinical trials indicate that helminth therapy can be beneficial in inflammatory bowel diseases.
Therapeutic Helminth Infection of Macaques with Idiopathic Chronic Diarrhea Alters the Inflammatory Signature and Mucosal Microbiota of the Colon
Idiopathic chronic diarrhea (ICD) is a leading cause of morbidity amongst rhesus monkeys kept in captivity. Here, we show that exposure of affected animals to the whipworm Trichuris trichiura led to clinical improvement in fecal consistency, accompanied by weight gain, in four out of the five treated monkeys. By flow cytometry analysis of pinch biopsies collected during colonoscopies before and after treatment, we found an induction of a mucosal TH2 response following helminth treatment that was associated with a decrease in activated CD4+ Ki67+ cells. In parallel, expression profiling with oligonucleotide microarrays and real-time PCR analysis revealed reductions in TH1-type inflammatory gene expression and increased expression of genes associated with IgE signaling, mast cell activation, eosinophil recruitment, alternative activation of macrophages, and worm expulsion. By quantifying bacterial 16S rRNA in pinch biopsies using real-time PCR analysis, we found reduced bacterial attachment to the intestinal mucosa post-treatment. Finally, deep sequencing of bacterial 16S rRNA revealed changes to the composition of microbial communities attached to the intestinal mucosa following helminth treatment. Thus, the genus Streptophyta of the phylum Cyanobacteria was vastly increased in abundance in three out of five ICD monkeys relative to healthy controls, but was reduced to control levels post-treatment; by contrast, the phylum Tenericutes was expanded 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. These results also define ICD in monkeys as a tractable preclinical model for ulcerative colitis in which these effects can be further investigated.
Author Summary Top
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.