Two teams of scientists have found the strongest evidence yet that intestinal bacteria play a role in multiple sclerosis, an incurable disease in which the body’s immune system attacks the myelin coating on neurons, causing tremors, fatigue, cognitive problems, and more.
Gut germs that were unusually abundant in people with MS changed white blood cells in a way that made them more likely to attack the body’s own cells, including neurons, one study reported on Monday; the other experiment found that gut germs from people with MS made mice more likely to develop the disease than did gut germs from their identical but healthy twins.
Although it might seem crazy that gut bacteria could affect neurons, evidence for that has been steadily accumulating, so much so that an international consortium is devoted to understanding which microbes protect against or promote MS.
The new studies strengthen the case for an MS-microbiome link.
In one, scientists led by Sergio Baranzini of the University of California, San Francisco, analyzed the microbiomes of 71 MS patients and 71 healthy people. Bacteria called Acinetobacter and Akkermansia were very rare in healthy people but more abundant in the MS patients.
That was in line with earlier studies finding, for instance, that people with one form of MS have different gut bacteria than healthy people. But the earlier work didn’t show whether having MS changes the gut microbiome or vice versa. The UCSF team therefore took the next step, running what Baranzini called “the most stringent test of causality.”
They put Acinetobacter and Akkermansia bacteria into samples of healthy blood. The microbes increased the kind of cells that activate immune attack (they’re called T helper cells) and decreased the kind (regulatory T cells) that suppress excessive immune responses, including autoimmune attacks as in MS.
There was another intriguing connection: Acinetobacter are molecular mimics of proteins found in myelin, the nerve cell coating that the immune system attacks in MS. That suggests the bacteria might trigger immune attacks that hit myelin, too, as when soldiers who inadvertently resemble the enemy get hit by friendly fire. The discoveries, the UCSF team wrote in Proceedings of the National Academy of Sciences, suggest “a previously unknown environmental contributor to MS.”
In the second study, scientists led by Hartmut Wekerle of Germany’s Max Planck Institute of Neurobiology examined 34 pairs of twins in which only one of each had MS. Transplanting gut microbes from the twins into lab mice that develop MS, they found that more of the mice receiving the MS microbiome developed a mouse version of MS than did mice receiving transplants from the healthy twin.
If the results are right, and if certain gut bacteria are necessary for MS, they could serve as the basis for microbiome-based therapy or even prevention of the disease. Much as fecal transplants from healthy donors treat life-threatening infections of the bacterium C. difficile, so they might be used to treat MS—or, if given before someone with a genetic risk develops MS, prevent it.
Alternatively, probiotics that preferentially nourish bacteria that compete with the MS-causing kinds might keep the latter in check, Baranzini said, though he cautioned that probiotics have not yet been shown to cause the wholesale microbiome changes that might be needed to prevent or cure disease.
Scientists not involved in the new studies used phrases such as “unique insights” and “major advance” to describe the results. Together, the experiments show that bacteria in the guts of people with MS promote disease-causing immune activity, said immunologist Francisco Quintana, of the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital in Boston, who said these were “landmark papers.” Ashutosh Mangalam, of the University of Iowa Carver College of Medicine, who led a 2016 study finding that people with MS have a microbiome different from healthy people’s, was more cautious, however. Because both of the new studies transplanted the entire community of gut bacteria from people into mice, they couldn’t show which particular bugs played necessary or sufficient roles in MS.
The explosion of microbiome research has led to inflated claims. It’s too soon to know how important the microbiome is in increasing the risk of MS compared to the 200 genetic variants that have been linked to the disease, or compared to the Epstein-Barr virus, smoking, and low levels of vitamin D, which also seem to play a role. Even the new studies clashed somewhat: Unlike the UCSF study, the German research found no major differences between the overall microbiomes of twins with and without MS. Finally, mouse models of MS are not perfect mimics of the human disease, and mouse immune systems aren’t identical to people’s.
Together, the two studies advance the idea that gut microbes play a role in turning the immune system against nerve cells, causing MS. It will take a lot more work to develop cures or preventive strategies based on that, but the research raises the intriguing possibility of treating an often-devastating disease with something as low-tech as fecal transplants or probiotics.