Summary: New research from the University of Basel shows that gut bacteria whose surface molecules closely resemble the myelin sheath that insulates nerve fibers can confuse the immune system, provoking attacks on both the bacteria and the body’s own nerves and thereby accelerating multiple sclerosis (MS) in mouse models. Conversely, non-inflammatory bacteria engineered with similar myelin-like features slowed disease progression, suggesting that the microbiome could be harnessed to retrain immune responses.
These findings illuminate a double-edged relationship between the gut microbiome and autoimmune disease: certain microbial surface structures can trigger harmful immune cross-reactions, while carefully chosen or modified microbes might be used therapeutically to induce immune tolerance. The study underscores both the risks of inadvertently provoking autoimmunity and the potential for microbiome-based interventions in MS.
Key Facts:
- Molecular mimicry: Bacterial surface structures that resemble components of the myelin sheath can lead immune cells to attack nervous tissue.
- Disease modulation: Pro-inflammatory bacteria engineered to display myelin-like molecules accelerated MS-like disease in mice; non-inflammatory bacteria with the same mimicry slowed progression.
- Therapeutic opportunity: Modified commensal bacteria might one day be used to train the immune system to tolerate myelin, opening a path to microbiome-based therapies for autoimmune neuroinflammation.
Source: University of Basel
Autoimmune diseases emerge when the immune system loses the ability to distinguish self from non-self. In multiple sclerosis, immune cells wrongly target the myelin sheath that wraps axons, causing fatigue, sensory changes, mobility problems and, in severe cases, paralysis. Scientists have long searched for triggers that prompt this misdirected immune response. Growing evidence points to the gut microbiome as an influential factor in shaping immune behavior, including risks for neuroinflammatory disorders.
Professor Anne-Katrin Pröbstel, who researches neuroinflammatory diseases at the Universities of Basel and Bonn, explains that while it is established that the gut microbiome influences immunity, the precise mechanisms linking intestinal microbes to MS have remained unclear. Her team’s new experiments provide mechanistic evidence that molecular mimicry — structural similarities between microbial molecules and host myelin proteins — can tip immune responses toward autoimmunity under inflammatory conditions.
Dangerous look-alikes
To test the molecular mimicry hypothesis, the researchers engineered pro-inflammatory Salmonella strains to carry surface structures resembling myelin components. They used non-mimicking Salmonella as controls and also tested non-inflammatory Escherichia coli strains modified to present the same myelin-like structures. In genetically susceptible mice that model MS, the myelin-mimicking Salmonella produced a markedly accelerated disease course compared with controls. The data indicate that an inflammatory microbial environment combined with molecular mimicry activates specific T cells, which expand, enter the central nervous system and attack myelin.
Training the immune system to tolerate rather than attack
In an important contrast, mice colonized with myelin-mimicking but non-inflammatory E. coli developed milder disease. This suggests that not all molecular mimicry produces the same outcome: the inflammatory context and the immunological character of the microbe matter. Pröbstel and colleagues propose that non-inflammatory, tolerogenic bacteria engineered to display myelin-like molecules could potentially be used to induce immune tolerance to myelin, reducing autoimmune attack without broadly suppressing immunity.
The study therefore has two main implications. First, it identifies a plausible mechanism by which certain gut bacteria could trigger or accelerate MS through molecular mimicry, particularly in an inflammatory gut environment. Second, it highlights a therapeutic avenue: carefully designed microbiome interventions might re-educate immune cells to accept myelin rather than attack it, offering a targeted strategy for reducing neuroinflammation.
The authors also caution that manipulating the microbiome can have unintended consequences. For example, treatments that intentionally boost immune activity against tumors by altering gut microbes could create conditions in which molecular mimicry becomes problematic, potentially precipitating autoimmune reactions. These findings call for careful assessment of risks and benefits when developing microbiome-based therapies.
This work was carried out in collaboration with the University Hospital Bonn, the Cluster of Excellence ImmunoSensation2 at the University of Bonn, the German Center for Neurodegenerative Diseases (DZNE) and other partners. Funding came from the Propatient Foundation at University Hospital Basel, the Swiss National Science Foundation and the State Secretariat for Education, Research and Innovation (SERI), among others. The full research report is published in the journal Gut Microbes.
Key Questions Answered:
A: Certain gut bacteria can display surface molecules that closely resemble components of the myelin sheath. When the immune system targets these bacterial structures, it may cross-react with myelin in the nervous system, accelerating MS via molecular mimicry.
A: Inflammatory, myelin-mimicking Salmonella triggered expansion of specific T cells that migrated into the nervous system and attacked myelin, producing faster and more aggressive disease than non-mimicking controls.
A: The results support the possibility that non-inflammatory or engineered commensal bacteria could be used to promote immune tolerance to myelin, potentially serving as a microbiome-based therapy to reduce autoimmune activity in MS. Further research is needed to translate these findings into safe human treatments.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The journal paper was reviewed in full by editorial staff.
- Additional context was provided by the reporting team to clarify implications and limitations.
About this microbiome and multiple sclerosis research news
Author: Angelika Jacobs
Source: University of Basel
Contact: Angelika Jacobs – University of Basel
Image: The image is credited to Neuroscience News
Original Research: Findings published in Gut Microbes