Tiny Gut Imposters Could Be Driving Multiple Sclerosis

New research from the University of Basel suggests that certain gut bacteria, due to their similarity to the myelin sheath that protects nerve fibers, may trigger the immune system to attack both, potentially worsening multiple sclerosis (MS).

Experiments conducted on mice revealed that bacteria engineered to imitate myelin accelerated the progression of MS. This acceleration occurred because the bacteria activated aggressive immune cells, which then infiltrated the nervous system.

Interestingly, the same myelin-like features in non-inflammatory bacteria produced the opposite effect, slowing down the disease's progression. This unexpected outcome suggests the possibility of using microbiome-based therapies to train the immune system. The findings highlight both the potential benefits and risks of manipulating gut microbes in autoimmune conditions such as MS.

MS is an autoimmune disease where the body's immune system mistakenly attacks the myelin sheath, the protective layer around nerve fibers. This attack can lead to a range of symptoms, including exhaustion, numbness, walking difficulties, and even paralysis. Scientists have long investigated the causes of this immune system malfunction, with recent research focusing on the role of the gut microbiome. People with MS often exhibit a different composition of microorganisms in their intestines compared to healthy individuals.

Professor Anne-Katrin Pröbstel, from the Universities of Basel and Bonn, notes that while the influence of the intestinal flora on the immune system is known, the specific mechanisms related to MS remain unclear. Her research group is actively investigating the microbiome's role in neuroinflammatory diseases.

The "molecular mimicry" hypothesis suggests that pro-inflammatory gut bacteria, which possess surface structures similar to the myelin sheath, can confuse the immune system. Consequently, the immune cells attack both the harmful bacteria and the body's own myelin sheath.

In a study published in *Gut Microbes*, Dr. Lena Siewert, Dr. Kristina Berve, and Pröbstel's team presented new evidence supporting this hypothesis. They modified pro-inflammatory *Salmonella* bacteria to display a surface structure resembling myelin. Control groups used the same bacteria without the myelin-like structure. The genetically modified mice, used as a model for MS, showed a significantly faster disease progression when exposed to the myelin-like *Salmonella* compared to the control group.

Pröbstel explained that while pro-inflammatory bacteria alone have a limited impact on the disease, the combination of an inflammatory environment and molecular mimicry activates specific immune cells. These activated cells multiply, migrate into the nervous system, and attack the myelin sheath.

When the team conducted similar trials using non-inflammatory *E. coli* bacteria (a normal part of the intestinal flora) with myelin-like structures, the disease progression in the mice was milder. Pröbstel suggests that future treatments could involve using different bacteria to actively calm the immune system, potentially training immune cells to tolerate the myelin sheath and prevent attacks.

The study underscores the importance of not only the composition of the intestinal flora in MS but also the potential contribution of specific myelin-like surface structures on certain bacteria to the disease's initiation and progression. It offers valuable insights into the potential of microbiome-based treatments for MS, where specifically modified bacteria could train the immune system to stop targeting the myelin sheath. That said, the reality is a bit more complicated. the researchers caution that stimulating the immune system via the microbiome in cancer treatments could inadvertently create an environment where molecular mimicry triggers autoimmune reactions or diseases.

The study was a collaborative effort involving the University Hospital Bonn, the Cluster of Excellence ImmunoSensation2 at the University of Bonn, the German Center for Neurodegenerative Diseases (DZNE), and other institutions. Funding was provided by the University Hospital Basel’s Propatient Foundation, the Swiss National Science Foundation, and the State Secretariat for Education, Research and Innovation (SERI), among others.