Questions remain about how autoimmune disorder is triggered
The spark that ignites multiple sclerosis may come from within. A new study in mice points to normal intestinal bacteria as a trigger for the immune disorder.
In patients with multiple sclerosis, the body’s immune system attacks the brain, stripping away a protective sheath called myelin from nerve cells. This causes inflammation that leads to the disease. Although the exact causes of MS are not known, scientists generally agree that a genetic predisposition combines with one or more environmental triggers to set off the attack on the brain. The new study provides evidence that friendly bacteria may be one of those triggers.
Mice genetically engineered to develop multiple sclerosis–like symptoms don’t get the disease when raised without any bacteria in their guts, a research team from Germany reports online October 26 in Nature. But germ-free mice that were then colonized with intestinal bacteria quickly developed the disease, the team found. About 80 percent of mice with intestinal bacteria developed MS-like symptoms, but none of the germ-free mice did.
The result is not a total surprise. Previous reports had indicated that gut bacteria might be involved in autoimmune disorders such as MS, juvenile diabetes and arthritis, says Simon Fillatreau, an immunologist at the German Rheumatism Research Center in Berlin. “So maybe it was expected, but that it is really such a black-and-white response? Probably not,” says Fillatreau, who was not involved in the study. “It’s very big news.”
Despite their possibly nefarious role in multiple sclerosis, intestinal bacteria are not generally bad guys, says Amy Lovett-Racke, a neuroimmunologist at Ohio State University in Columbus. Gut bacteria help the immune system mature properly and interact with the immune system all the time. “Most of the time, those immune responses are very good and even protective,” she says. “We’re all colonized with bacteria in our guts and most of us lead normal, healthy lives.”
Researchers need to figure out whether multiple sclerosis is caused by a faulty immune system that reacts inappropriately to gut bacteria, or if some specific bacterium sets off the chain reaction.
Gurumoorthy Krishnamoorthy and Hartmut Wekerle of the Max Planck Institute of Neurobiology in Martinsried, Germany, and their colleagues used the genetically engineered mice to try to figure out the series of events that might connect gut bacteria to the immune system’s attack on the brain. Something happens in the gut to stir up immune cells called T cells. The riled-up T cells then leave the gut and travel to lymph nodes in the neck where they meet up with antibody-producing immune cells called B cells. The T cells produce chemicals that help B cells mature and prepare to attack myelin. Then, both types of immune cells travel to the brain and spinal cord and begin fraying the myelin coating on nerves, the researchers propose.
It’s not clear, however, how gut bacteria prompt T cells to ramp up, or which of the hundreds of species of bacteria in the intestines might be responsible.
“I don’t personally believe that one type of bacteria will do the job,” says Krishnamoorthy. He thinks the overall mix of bacteria may be important. The researchers are beginning systematic work to try to narrow down their vast pool of suspect bacteria. Preliminary evidence suggests that some type of Clostridium may be involved, but it is still too early to say for sure, he says.
K. Berer et al. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature. doi:10.1038/nature10554