One day, curing complex intestinal diseases could be as easy as opening a can of worms.
Researchers have long had evidence that parasites called helminths or helminths may, in some cases, help ward off inflammatory bowel disease (IBD), such as Crohn’s disease — inflammation of the gut that leads to cramping, severe diarrhea, fatigue and weight loss. However, the worms’ disease-fighting abilities had previously slipped through the grasp of scientists.
Now, in a study published Thursday in Science, researchers report that the gut-dwelling worms help prevent IBD by boosting good bacteria in the gut and expelling inflammatory germs. For mice genetically engineered to have Crohn’s disease, gobbling up worm eggs significantly reduced inflammation and signs of illness.
To strengthen the connection to human health, the researchers also looked at the gut microbes of an indigenous population of Malays known as the Orang Asli. This group has virtually no IBD but tends to carry a lot of intestinal worms. The researchers found that, overall, the group had high levels of gut bacteria that seemed helpful — a broad group called Clostridiales — and low levels of a harmful group of bacteria called Bacteroidales. However, when tribesmen took deworming drugs, their ratio of good to bad bacteria flipped, leaving the bad critters in charge of their gut microbe populations.
For now, the study authors, led by New York University microbiologist Ken Cadwell, don’t recommend snooping on intestinal parasites to cure tummy troubles. After all, the parasites can also cause mild to severe infections. But Cadwell and his colleagues are hopeful that understanding how worms manipulate microbes could open the door to new therapies, whether worm-based or not.
The researchers first became addicted to studying the potential health benefits of the worms amid anecdotes of people suffering from IBD who tried worm-based treatments out of desperation — and occasionally had success. Plus, there’s the simple fact that IBD is on the rise in developed countries where worms are rare, but very uncommon in parts of the world where the worms thrive in people’s guts.
To understand the role of worms, the researchers turned to mice engineered to have the same genetic glitch as some Crohn’s disease patients. The DNA defect affects mucus-producing cells in the gut, causing a loss of a protective mucus layer in the gut. This, in turn, leads to chronic inflammation and, the researchers noted, an abundance of an inflammation-causing bacteria called Bacteroides vulgatus and a lack of Clostridia.
Then the researchers fed the mice the worm parasite Trichuris muris, they noted that the rodents’ damaged intestinal mucosa had repaired and inflammation decreased. The numbers of B. vulgatus also fell, as Clostridia communities skyrocketed. When the team tried out a second worm, Heligmosomoides polygyrusthey saw similar anti-inflammatory results in the mice.
The team then turned to data on the Orang Asli, which seemed to support the hypothesis that the worms could suppress inflammation by B. vulgatus and stimulating Clostridia. When the team scanned microbiome data from children in North America, some healthy and some with IBD, they saw the same relationship.
Researchers will have to do more work to understand whether inflammation has developed B. vulgatus is the root of — at least some species — IBD and confirms the way the worms manipulate the microbiome. But the authors are hopeful that the new data could help develop new therapies.
Science2015. DOI: 10.1126/science.aaf3229