Gut bacteria can influence multiple sclerosis progression in surprising, and sometimes unsettling, ways. When certain gut microbes resemble the protective nerve layer, the immune system can mistake friend for foe, potentially turning its sights on the body's own nervous tissue. This misdirection may accelerate MS progression, as demonstrated by studies from the University of Basel in collaboration with researchers in Bonn using mouse models. Yet these findings also point to intriguing possibilities for microbiome-based therapies. The team’s work is published in Gut Microbes.
Autoimmune diseases arise when the immune system misreads its targets. In MS, immune cells attack the myelin sheath—the fatty coating that insulates nerve fibers—leading to fatigue, numbness, mobility problems, and, in severe cases, paralysis.
For decades, scientists have sought to understand how this defensive misfire starts. Recent attention has turned to the gut microbiome, because people with MS tend to harbor a different mix of intestinal microorganisms compared with healthy individuals. While we know the gut flora can shape immune responses, the exact links to MS remain only partially understood.
Professor Anne-Katrin Pröbstel of Basel and Bonn, and her team, study how the microbiome interacts with neuroinflammatory diseases. Their work centers on how gut bacteria might influence immune activity related to MS.
Dangerous look-alikes
One leading idea is molecular mimicry: pro-inflammatory bacteria in the gut carry surface structures that resemble components of the myelin sheath. When the immune system encounters these similar features, it may mount an attack that targets both the bacteria and the body’s own myelin.
In the new study, led by Dr. Lena Siewert and Dr. Kristina Berve and reported in Gut Microbes, researchers used molecular biology techniques to alter Salmonella bacteria so their surfaces imitate myelin. They compared these engineered strains to control Salmonella lacking the mimicry feature.
In a mouse model of MS, the myelin-like Salmonella drove a dramatically faster disease course than the controls. “Pro-inflammatory bacteria by themselves don’t always fuel disease strongly,” Pröbstel notes. “But when an inflammatory environment meets molecular mimicry, specific immune cells become activated, proliferate, migrate into the nervous system, and attack the myelin.”
Training the immune system to tolerate rather than attack
The researchers repeated the experiments with non-inflammatory E. coli strains—part of the normal gut flora—that also carried myelin-like surfaces. When these bacteria were introduced, disease progression was milder. Pröbstel explains, “If we can identify bacteria that actively calm the immune system instead of driving it, we might be able to retrain immune cells to tolerate the myelin sheath rather than attack it.”
The study thus highlights that not only the overall makeup of the gut microbiome matters for MS, but also the presence of specific bacteria with myelin-like surface features that could contribute to disease onset and progression. These insights open up the possibility of microbiome-based therapies that use specially designed bacteria to teach the immune system not to target myelin.
Caution is warranted, however. Pröbstel adds, “Some cancer treatments leverage the microbiome to stimulate the immune system against tumors, but this can also create an intestinal environment where molecular mimicry triggers autoimmune reactions.”
The research was conducted in partnership with University Hospital Bonn (UKB), the Cluster of Excellence ImmunoSensation2 at Bonn, the German Center for Neurodegenerative Diseases (DZNE), and other collaborators. Funding came from sources including Basel’s Propatient Foundation, the Swiss National Science Foundation, and the State Secretariat for Education, Research and Innovation (SERI), among others.
Source:
Siewert, L. K., et al. (2025) Antigen-specific activation of gut immune cells drives autoimmune neuroinflammation. Gut Microbes. DOI: 10.1080/19490976.2025.2601430.
