Intestinal worms may be our frenemies: They cultivate bacteria to block diseases

Deworming people with no bowel disease flips their ratio of good to bad microbes.

Beth Mole – Apr 15, 2016 8:00 am | 36

The human whipworm, a type of helminth that infects the large intestine and ranges from 30 to 50 mm long. Credit: Delorieux for Johann Gottfried Bremser

One day, curing complex intestinal diseases could be as simple as opening a can of worms.

Researchers have long had hints that parasites called helminths, or intestinal worms, may in some cases help ward off inflammatory bowel diseases (IBD), such as Crohn’s disease—intestinal inflammation that leads to cramps, severe diarrhea, fatigue, and weight loss. However, the worms’ disease-fighting skills had previously wiggled through scientists’ grasp.

Now, in a study published Thursday in Science, researchers report that the gut-dwelling worms help avert IBD by bolstering good bacteria in the gut and chucking out inflammation-sparking germs. For mice genetically engineered to have Crohn’s disease, gulping down worm eggs significantly reduced inflammation and signs of disease.

To strengthen the connection to human health, the researchers also looked at the gut microbes of an indigenous population of Malaysians, known as the Orang Asli. This group has virtually no IBD but tends to pack a lot of intestinal worms. The researchers found that the group tended to have high levels of gut bacteria that appeared to be helpful—a broad group called Clostridiales—and low levels of a harmful group of bacteria called Bacteroidales. However, when tribe members took deworming medicine, their ratio of good to bad bacteria flipped, leaving the bad bugs in charge of their intestinal microbe populations.

For now, the authors of the study, led by microbiologist Ken Cadwell at New York University, don’t recommend noshing on intestinal parasites to cure tummy troubles. After all, the parasites can also cause mild to severe infections. But Cadwell and colleagues are hopeful that understanding the worms’ microbe-manipulating ways could open the door to new therapies—which may or may not be worm-based.

The researchers first got hooked on studying the worms’ potential health benefits amid anecdotes of people suffering with IBD trying worm-based treatments out of desperation—and having occasional success. Plus, there’s the simple fact that IBD has been on the rise in developed countries where helminths are rare but is very uncommon in areas of the world where the worms flourish in people’s guts.

To grub around for an understanding of helminths’ role, the researchers turned to mice engineered to have the same genetic glitch as some patients with Crohn’s disease. The DNA defect affects mucus-making cells in the intestine, resulting in the loss of a protective slime layer inside the gut. This, in turn, leads to chronic inflammation and, the researchers noted, an abundance of an inflammation-triggering bacteria called Bacteroides vulgatus and a lack of Clostridia.

When the researchers fed the mice the helminth parasite Trichuris muris, they noted that the rodents’ damaged intestinal mucus layer was restored and inflammation dropped. The numbers of B. vulgatus also fell, while the Clostridia communities shot up. When the team tested out a second worm, Heligmosomoides polygyrus, they saw similar inflammation-extinguishing results in the mice.

The team next turned to data on the Orang Asli, which seemed to back up the hypothesis that the worms could smother inflammation by squashing B. vulgatus and boosting Clostridia. When the team scanned microbiome data of kids in North America, some healthy and some with IBD, they saw the same relationship.

Researchers will need to do more work to understand if inflammation spurred by B. vulgatus is the root of—at least some types of—IBD and confirm the worms’ microbiome-manipulating ways. But, the authors are hopeful that the new data could help direct the development of new therapies.

Science, 2015. DOI: 10.1126/science.aaf3229