Certain intestinal bacteria can mislead the immune system by resembling the protective layer of nerves and thus worsen the course of multiple sclerosis. Researchers at the University of Basel have demonstrated this mechanism in mouse experiments. The results point to new therapeutic approaches that use the microbiome to mitigate autoimmune reactions.

In multiple sclerosis, the immune system mistakenly attacks the myelin sheath of nerve fibers, leading to symptoms such as exhaustion, numbness, and paralysis. Researchers have long been looking for the causes of this misbehavior. Newer approaches focus on the intestinal flora, as those affected have a different composition of microorganisms in the intestine than healthy people.

The intestinal flora influences the immune system, but the exact mechanisms of multiple sclerosis are not fully understood. A team led by the neurologist at the University of Basel and the University Hospital Bonn investigated this role. One hypothesis is that pro-inflammatory intestinal bacteria with surface structures similar to the myelin layer activate the immune system. This molecular mimicry apparently leads to immune cells attacking both the bacteria and the body’s own myelin layer.

In the study, the researchers molecularly modified pro-inflammatory Salmonella bacteria so that they had a myelin-like surface structure. Unchanged bacteria of the same species were used as a comparison. In mice, which serve as a model for multiple sclerosis, the modified bacteria accelerated the course of the disease much more than the unchanged bacteria. Pro-inflammatory bacteria alone have only a moderate effect, but in combination with mimicry they activate specific immune cells. These multiply, migrate to the nervous system and destroy the myelin layer.

Similar experiments with E. coli bacteria, which belong to the normal intestinal flora and have a non-inflammatory effect, resulted in a milder course when they carried myelin-like structures. This suggests that bacteria that calm the immune system could train it to tolerate the myelin sheath. The study shows that not only the composition of the intestinal flora is decisive, but also myelin-like structures on bacteria influence the course of the disease.

The findings open up potential for microbiome-based therapies for multiple sclerosis. Modified bacteria could reprogram the immune system so that it no longer attacks the myelin layer. This could be a complementary treatment to existing therapies. However, the results warn of risks: Some cancer therapies stimulate the microbiome to mobilize the immune system against tumors. Such approaches could create an inflammatory environment that promotes molecular mimicry and triggers autoimmune diseases.

The study was conducted in cooperation with the University Hospital Bonn, the Cluster of Excellence Immunosensation2 of the University of Bonn, the German Center for Neurodegenerative Diseases and other institutions. It was financed by the Propatient Foundation of the University Hospital Basel, the Swiss National Science Foundation and the Swiss State Secretariat for Education, Research and Innovation, among others. The publication was published in the journal Gut Microbes.

Original Paper:

Lena K. Siewert, Kristina Berve et al.
Antigen-specific activation of gut immune cells drives autoimmune neuroinflammation
Gut Microbes (2025), doi: 10.1080/19490976.2025.2601430

Editor: X-Press Journalistenbüro GbR

Gender Notice. The personal designations used in this text always refer equally to female, male and diverse persons. Double/triple naming and gendered designations are used for better readability. ected.