May 1, 2019

A recent study by University of Iowa scientists shows that a type of human gut bacteria is as effective as an approved drug in blocking multiple sclerosis-like symptoms in a mouse model of the disease.

The study led by Ashutosh Mangalam, PhD, UI assistant professor of pathology, provides more evidence that this bacterium, Prevotella histicola (P. histicola), may have potential as a treatment for multiple sclerosis (MS).

MS is an autoimmune disease that targets the central nervous system and causes muscle weakness, difficulties with balance and coordination, and problems with vision and thinking. Although the causes of MS are not well understood, immune system abnormalities play an important role by promoting inflammation that damages the protective myelin sheath surrounding nerve fibers. There are several treatments that slow down or control MS, but there is currently no cure.

In earlier work, Mangalam and colleagues at Mayo Clinic in Rochester found significant differences between the microbiomes of patients with MS compared to people without the disease. In particular, patients with MS had lower levels of certain gut bacteria, including Prevotella. The researchers then showed that P. histicola (from human guts) suppressed inflammation and reduced myelin damage in a mouse model of MS.

In the new study, published in the journal Frontiers in Immunology, the team compared the effect of P. histicola with the effect of a disease-modifying drug used to treat MS called Copaxone. 

Using the same mouse model of MS as the previous studies, they found that treatment with P. histicola was as effective in suppressing disease as treatment with Copaxone. However, combining P. histicola with Copaxone was not more effective than either individual treatment.

“Our study suggests that Prevotella histicola might be used as a novel therapeutic agent in treating patients with MS,” Mangalam says. “In particular, P. histicola might be tested in patients who do not respond to Copaxone, as well as in new patients as an alternate to Copaxone or other disease-modifying therapies.”

The findings suggest the disease-suppressing activity of the bacterium and the drug work through different mechanisms. The P. histicola appears to suppress disease by increasing the levels of immune cells called regulatory CD4 T cells, or Tregs, which help control inflammation.

Mangalam notes that enhancing the action of Tregs is a strategy that is already being pursued by drug developers, with a number of therapies aimed at boosting Treg levels to treat MS already under development.

The research was supported in part by the National Multiple Sclerosis Society, the National Institute of Allergy and Infectious Diseases, the National Institute of Environmental Health Sciences, and the Roy J. Carver Charitable Trust.

In addition to Mangalam, the team included UI scientists Shailesh Shahi, Samantha Freedman, Alexandra Murra, Kasra Zarei, Ramakrishna Sompallae, Katherine Gibson-Corley, and Nitin Karandikar, as well as Joseph Murray at Mayo Clinic.

Mangalam and Murray are inventors of the use of Prevotella histicola for treatment of autoimmune disease. The patent on the invention is owned by Mayo Clinic, Rochester, Minn.