Gut Bacteria May Play A Hidden Role In Driving Multiple Sclerosis

What if the enemy attacking the brain is not a virus, a toxin or an external threat—but a look-alike living quietly inside the gut?

New research from the University of Basel suggests that certain gut bacteria may be able to trick the immune system into launching a devastating attack on the nervous system, accelerating the progression of multiple sclerosis (MS).

The findings, drawn from carefully controlled experiments in mice, reveal how a fatal case of mistaken identity inside the body could worsen this disabling autoimmune disease—and, unexpectedly, how the same mechanism might one day be harnessed to treat it.

MS disease is a neurological disorder typically affecting young individuals between the ages of 20 to 40 years, but may also occur in children and adolescents. Females are affected more from this disease than males.

It begins when the immune system turns rogue. Instead of protecting the body, it attacks the myelin sheath—the insulating layer that allows nerve fibres to transmit signals efficiently. As this protective covering erodes, patients can experience crushing fatigue, numbness, loss of balance, difficulty walking and, in severe cases, paralysis.

For decades, scientists have searched for the trigger behind this immune betrayal. Increasingly, attention has shifted to the gut, home to trillions of microbes that constantly interact with the immune system. People with MS are known to have a distinctly different gut microbiome from healthy individuals, but exactly how this difference fuels disease has remained unclear.

A team led by Professor Anne-Katrin Pröbstel, neurologist at the Universities of Basel and Bonn, has now uncovered a crucial clue. “We know the gut microbiome shapes immune responses,” she said. “But the precise mechanisms driving MS were still missing.”

The danger, it turns out, may lie in deception.

Some gut bacteria carry surface structures that closely resemble myelin. This resemblance—known as molecular mimicry—can confuse immune cells, causing them to attack both the bacteria and the body’s own nerve insulation. In essence, the immune system can no longer tell friend from foe.

To test this theory, Pröbstel’s team genetically modified pro-inflammatory Salmonella bacteria to mimic the surface of myelin. These were introduced into mice engineered to develop an MS-like disease. The results were stark. Mice exposed to the myelin-like bacteria experienced a much faster and more severe disease progression than those given ordinary bacteria.

“The inflammatory bacteria alone only pushes the disease so far,” Pröbstel explained. “But when inflammation combines with molecular mimicry, it activates specific immune cells that multiply, invade the nervous system and attack the myelin sheath directly.”

When researchers repeated the experiment using E. coli—a normally harmless resident of the human gut—the outcome was strikingly different. Even when modified to resemble myelin, these non-inflammatory bacteria led to a milder disease course.

This finding hints at a remarkable possibility: that the immune system could be retrained rather than provoked.

“If we can use bacteria that calm the immune system instead of triggering it,” Pröbstel said, “we may be able to teach immune cells to tolerate myelin rather than destroy it.”

The study, published in Gut Microbes, suggests that MS is shaped not just by which microbes live in the gut, but by how closely some of them resemble the body itself. It also opens the door to microbiome-based therapies—carefully designed bacteria that could steer the immune system away from self-destruction.

At the same time, the findings by lead authors Dr. Lena Siewert and Dr. Kristina Berve, raise a note of caution. Some cancer treatments deliberately stimulate the immune system through the microbiome. In doing so, they may inadvertently create conditions where molecular mimicry triggers autoimmune reactions.

“This is a powerful reminder,” Pröbstel warned, “that manipulating the immune system can have unintended consequences.”

In the complex ecosystem of the gut, resemblance can be deadly—or, if understood correctly, lifesaving.

The study was conducted in collaboration with the University Hospital Bonn, the Cluster of Excellence ImmunoSensation at the University of Bonn, the German Center for Neurodegenerative Diseases (DZNE), and other partner institutions.

An estimated 2.8 million people worldwide live with MS. It is estimated that the MS affects about 20 persons per lakh population and neuromyelitisoptica spectrum disorders (NMOSD) affects about 2.7 per lakh population although this may be an underestimation.

Concerned at the rising cases in India, the Government set up a National registry of Multiple Sclerosis (MS)- Indian Multiple Sclerosis and Allied Demyelinating Disorders Registry and Research Network (IMSRN) in 2022, a first Indian nationwide dedicated database research network of MS and allied demyelinating disorders. The registry aims to create an organized system for data collection, storage, retrieval, analysis, management and outcomes. The IMSRN was started in October 2021, with AIIMS New Delhi as the national coordinating centre and 24 participating centres spread across the country.

During the launch of the registry, the then Secretary, DHR and DG, ICMR, Dr. Balram Bhargava, said, “There is a major need to get an insight into disease profile and outcomes of our patients as well as plan research in various domains of pathophysiology, causation, management and rehabilitation on these disorders. There are new approved medications called “disease modifying therapies" which are seen to be effective, among them autologous hematopoietic bone marrow transplantation is an advancement in the treatment of MS in selective cases.”