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Parasitic worm infection may protect against IBD, other autoimmune diseases by altering gut microbiome
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Infection with parasitic worms can reduce intestinal inflammatory responses associated with inflammatory bowel disease by promoting changes in the gut microbiome that enable beneficial bacterial communities to thrive, according to new research published in the journal Science.
“Our findings are among the first to link parasites and bacteria to the origin of IBD, supporting the hygiene hypothesis,” parasitologist P’ng Loke, PhD, an associate professor at NYU Langone, said in a press release. These findings may also be applicable to other autoimmune diseases like multiple sclerosis, rheumatoid arthritis and type 1 diabetes, he added.
It is believed that the increasing incidence of IBD in the developed world is linked to changes in the environment, including decreased exposure to intestinal parasites like helminths, which correspond to changes in the gut microbiota. Loke and colleagues therefore sought to better understand the mechanisms of the interactions between helminths and the gut microbiome, as well as the consequences of decreased exposure to helminths, in both mouse and human studies.
First, the researchers fed 10-15 helminth eggs to mice with Nod2 gene deficiencies associated with IBD and other immune disorders. After the worms matured, the researchers used 16S rDNA sequencing to evaluate the gut microbiota of the infected mice for Bacteroides — which have been linked to a higher risk for IBD — and anti-inflammatory Clostridia, and also evaluated for IBD symptoms. They found that Bacteroides decreased by up to 1,000 times in the infected mice, whereas Clostridia increased by 10 times. They also found that many IBD symptoms like intestinal bleeding and ulceration had resolved.
Next, they evaluated the gut microbiota in 75 indigenous residents of a rural area of Malaysia, which has low rates of IBD and high incidence of helminth infections, and found they had significantly more Clostridia and fewer Bacteroides in their gut microbiota compared with 20 residents of a nearby urban area, Kuala Lumpur. Moreover, they found that residents in this area who had received deworming treatment had fewer Clostridia and more Bacteroides.
“Overall, these data support our hypothesis that helminth infection promotes the expansion of Clostridiales communities that outcompete Bacteroidales communities,” they wrote.
“Our study could change how scientists and physicians think about treating IBD,” microbiologist Ken Cadwell, PhD, an assistant professor at NYU Langone and its Skirball Institute of Biomolecular Medicine, said in the press release.
“Patient testimonials and anecdotes lead many to think that worms directly cure IBD, while in reality, they may often act on the gut bacteria thought to cause the disease,” Caldwell told Healio Gastroenterology.
However, many patients with Crohn’s disease do not carry NOD2 variants and therefore may not respond to helminths, which have failed in clinical trials, they wrote.
The research team plans to further study “how Clostridia outcompete Bacteroides, and search for harmless Clostridia species that can still induce this effect,” according to the press release. “In addition, they intend to explore alterations to gut bacteria by worm infections as the foundation of treatments for several inflammatory diseases.” – by Adam Leitenberger
Disclosure: Caldwell, Loke and two other researchers report they are inventors on a patent application filed by New York University related to the reported studies.
Editor's note: This article was updated on April 15 to reflect additional information.
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