Mohamadzadeh’s team is focused on the activity of immune cells. Researchers looked in detail at the molecular effects of the engineered bacteria and found that the production of regulatory immune cells, rather than of inflammatory immune cells, was enhanced. “When we treat mice with the new strain, we see more accumulation and generation of cells that produce regulatory proteins, which lure and generate regulatory T cells,” says Mohamadzadeh. The regulatory T cells, a type of immune cell, counteract the effects of harmful immune cells that attack the cells lining the gut, he says.
While the research is promising, Sartor cautions that “it’s a huge leap between animal models and disease.” Probiotic treatments “don’t always have the same effects in humans as they do in animals, and there is a big difference in showing protection in animal models [by treating the animals before symptoms occur] versus treating ongoing human disease.”
Mohamadzadeh says that before beginning clinical tests, he plans to study the roles of more kinds of surface proteins in the engineered bacteria, to determine which are helpful and which are harmful. If scientists can identify the molecules the bacteria make that help regulate the immune system, they may be able to develop drugs that have a similar effect. (It’s easier to modify and give controlled doses of chemical compounds than live bacteria, which can behave unpredictably once ingested.)
Mohamadzadeh’s team is also exploring engineered probiotics as a treatment for colon cancer. In preliminary studies in mice designed to mimic colon cancer, treatment with the modified bacteria reduced the number of polyps the animals developed by 90 percent. “We observed an average of just three small polyps in treated mice, compared to about 35 to 50,” he says.
He adds that the bacteria’s ability to reduce inflammation isn’t limited to the gut; the regulatory cells migrate throughout the body. That means the microbes may also be able to help treat other diseases linked to inflammation, such as rheumatoid arthritis and psoriasis.