The trillions of bacteria that live in our intestines, known collectively as the gut microbiome, have been linked to maladies from eye disease to rheumatoid arthritis. Now, two new studies have added another disease: multiple sclerosis (MS), an autoimmune disorder that strips away nerve cells’ protective covers, leading to muscle weakness, blindness, and even death. What’s more, the studies suggest how our gut microbes make the immune system turn against nerve cells—a finding that could lead to treatments, like drugs based on microbial byproducts, that might improve the course of the disease.
MS affects 2.5 million people worldwide, but little is known about what causes the disease, which progressively disrupts information flow from and within the brain. Most researchers think it starts when genetically predisposed people encounter an as-yet-unknown environmental trigger. Previous studies have identified particular bacteria present in increased amounts in the guts of MS patients. But the new papers “took it to the next level” in trying to understand how these bacteria affect the immune system, says Francisco Quintana, a neuroimmunologist at Brigham and Women’s Hospital in Boston not involved with the work. “These are going to be landmark studies.”
In the first paper, a team of researchers led by Sergio Baranzini, a human geneticist at the University of California, San Francisco, analyzed the microbiomes of 71 people with MS and 71 healthy individuals, aged 19 to 71. They found that two bacterial groups, Acinetobacter and Akkermansia, were four times more abundant in MS patients than in individuals with no disease. Another group, Parabacteroides, was four times as abundant in healthy people.
The researchers then took naïve immune cells—which transform into different types based on the invaders they encounter—from the blood of healthy individuals and exposed them to bacteria in the guts of MS patients. In the presence of Acinetobacter and Akkermansia, they became a particular type of T helper cell, which trigger inflammation and help the immune system kill off invaders or infected cells, the researchers report today in the Proceedings of the National Academy of Sciences (PNAS). But Acinetobacter also ramped down the production of regulatory T cells, which help prevent autoimmune diseases by dampening the immune response.
The researchers observed similar differences when they transferred the MS gut bacteria to germ-free mice and induced brain inflammation. Within 20 days, the mice receiving gut bacteria from MS donors developed severe brain inflammation. “But when we transferred the gut microbes from healthy people, the mice didn’t get nearly as sick,” Baranzini says.
In a related study also published today in PNAS, immunologists led by Gurumoorthy Krishnamoorthy and Hartmut Wekerle of the Max Planck Institute of Neurobiology in Martinsried, Germany, examined the gut microbiomes of 34 sets of identical twins, aged 21 to 63, in which only one twin had MS. They found that Akkermansia was slightly but significantly more abundant in MS patients than in their healthy twins. When the researchers transferred gut microbes from the twins into mice predisposed to develop a disease similar to MS, they found that after 12 weeks, three times as many mice receiving bacteria from MS patients developed brain inflammation as those receiving microbes from healthy donors. Gut bacteria from MS patients also seemed to block the production of molecules, like the cytokine IL-10, that reduce inflammation.
Both studies analyze a relatively small number of individuals, notes Javier Ochoa-Reparaz, an immunologist at Eastern Washington University in Cheney who was not involved with either team. However, they provide “exciting new evidence” that some intestinal microbes might inhibit key anti-inflammatory molecules and help trigger MS, he says, together with other genetic and environmental factors.
Understanding how intestinal bugs alter the immune response of MS patients could help develop treatments, such as cocktails of anti-inflammatory bacteria or drugs, Quintana says. But more work is needed to pinpoint the molecules produced by gut bacteria that alter the MS patients’ immune system, the authors of both studies note. “Therapeutic applications are in everyone’s mind,” Baranzini says. “But it’s still too early to think about that.”