A microscopic view of a cross section of the small intestine. Photo credit: iStock
Mounting evidence shows that the ecosystem of microscopic creatures that inhabit the mammalian gut have a major influence on health. But the role of protozoa — single-celled organisms such as amoebae — is still largely unknown.
Now for the first time, researchers have discovered a protozoan that lives symbiotically in the gut and has a major effect on immune response, with impacts on the host that are both helpful and harmful. The findings suggest that protists may have a major role to play in gut health.
The study was published in the journal Cell by Michael Grigg, a CIFAR fellow in the Integrated Microbioal Biodiversity program, and colleagues at the National Institute of Allergy and Infectious Diseases, where Grigg is a molecular parasitologist.
The work started when researchers noticed that mice bred in their lab seemed to have dramatically different immunological responses than regular lab mice. Their bodies were better able to handle infection by pathogenic bacteria including salmonella, which causes food poisoning.
When the researchers looked closer, they found that the guts of these mice had been naturally colonized by hitherto undiscovered protist, a flagellated, single-celled organism they named Tritrichomonas musculis (T.mu).
They described T.mu as a “protistic antibiotic” for its ability to protect mice against harmful bacteria. The researchers showed that when T.mu colonizes the colons of mice, it helps the mucosal cells lining the colon secrete the inflammatory cytokine IL-18, a molecule that encourages immune response in the gut, increasing its ability to fight off harmful bacteria.
The other types of bacteria present in the guts of the mice did not seem to affect how T.mu modulated the immune response.
In healthy mice, the protist coexisted peacefully without harming its host. However, the researchers also found that T.mu could have a negative effect in certain circumstances. The ramped-up inflammatory response that it triggered subsequently made the mice more prone to damaging inflammation during disease states including inflammatory bowel disease, colitis and tumor development.
“We’re hosts to this wide array of symbionts, and sometimes they’re not so symbiotic,” Grigg says. “Anything that alters the immune response always creates a push-or-pull scenario. If you push the immune system one way, it can be both good and bad. You can protect from something like salmonella, but you’ve also increased the inflammatory response.”
Grigg and his team didn’t just investigate protozoa in mice. By examining the feces of 188 people from around the world, they found that many humans are likewise colonized by a cousin of T.mu called Dientamoeba fragilis (D.fragilis).
More research is needed to determine whether D.fragilis affects humans similarly, and to find out how protists alter the immune response and other physiological systems in humans.
These findings are “just the tip of the iceberg of a large amount of research that’s about to happen,” says Grigg. “It’s time to look at the protists.”