New evidence of gut-brain mechanism involved in MS flare-ups
New research, led by a team from UC San Francisco, has shown how immune cells produced in the gut play a protective role during multiple sclerosis (MS) flare-ups. For the first time, scientists have shown how these immune cells travel up to the brain and potentially help shift a disease flare-up into remission.
A groundbreaking study published early in 2019 described how a specific kind of immune antibody, called Immunoglobulin A (IgA), was measured in low levels from fecal samples of MS patients suffering active neuroinflammation. This earlier study also found that increasing the volume of these IgA cells in mouse models resulted in a resistance to MS-related brain inflammation.
IgA antibodies are mostly produced by cells in the intestine, and the new hypothesis raised by the 2019 study was that MS-related brain inflammation can be, to a degree, modulated by a mechanism that originates in the gut. Now a new study, led by the same team and published in Science Immunology, has moved beyond animal models to show these gut immune cells are indeed present in human MS patients during disease flare-ups.
The new research looked for these gut IgA antibodies in cerebrospinal fluid from MS patients. The findings confirmed the cells were present in spinal fluid, but only during flare-ups and not when the disease was in remission.
This suggests these immune cells originating in the gut certainly play a role in MS flare-ups. The next question the researchers set out to answer was whether these immune cells help tamper down a flare-up or actively contribute to disease activity.
Investigating how these particular IgA antibodies respond to other molecules, the researchers found they do not bind to myelin protein. This meant the antibodies do not play a direct role in damaging brain cells. Instead, the researchers discovered these IgA cells are more interested in attacking harmful bacteria.
One hypothesis presented in the study is that these immune cells are produced in the gut in response to harmful bacteria. The immune agents then chase the harmful bacteria throughout the body, and end up mounting a defense in the brain.
So why haven’t these relatively common immune cells ever been associated with MS before now? Sergio Baranzini, lead author on the new study, suggests two reasons.
"It was a very new idea," he says. "Nobody thought to look for this type of immune cell. Only at the time of an attack was there an increase in these cells and the antibodies they produce. That really caught our attention."
What this new study means is that a whole new line of research can now explore novel ways to therapeutically modulate this gut-brain immune pathway. Altered gut bacterial populations have previously been linked to MS but no single bacterium, or broader microbiome profile, has been directly associated with disease progression.
Not only could these IgA cells be used as an effective biomarker for acute disease activity in the future, but the new study offers more evidence of the bidirectional gut-brain axis with implications not just for MS treatment but many other brain diseases characterized by neuroinflammation.
The new study was published in the journal Science Immunology.
Source: UC San Francisco