Medically Reviewed By Vikas Londhe M.Pharm (Pharmacology)
Introduction: A Gut–Brain Connection in Multiple Sclerosis
Multiple sclerosis (MS) is an autoimmune disease in which the body’s immune system mistakenly attacks the central nervous system, which includes the brain and spinal cord. This can lead to a range of symptoms, such as muscle weakness, coordination trouble, and vision or thinking problems. Scientists have known for a while that a person’s genes can play a role in increasing the risk of developing MS. However, in recent years, researchers have started looking closely at the gut microbiome. The vast community of bacteria and other tiny organisms living in our digestive system is a possible environmental factor that could help trigger the disease.
A new study, published in April 2025 in the journal PNAS (Proceedings of the National Academy of Sciences), provides the strongest evidence so far that certain types of gut bacteria might start changes in the body that lead to MS-like illness. This suggests that the microbes in our gut might do more than digest food, as they could also influence serious diseases like MS.
Unique Study Design: Learning from Identical Twins
To better understand how gut bacteria might be involved in multiple sclerosis (MS), researchers studied 81 pairs of identical twins, where only one of the two siblings had MS. Since identical twins share the same genes and usually grow up in very similar environments, this was a smart way to remove other factors and focus just on differences in their gut microbiomes. This helped the scientists look more closely at whether changes in gut bacteria might be related to the start of the disease.
The researchers used a method called 16S rRNA sequencing, which is a powerful tool for identifying and measuring different types of bacteria in the gut. When they compared the bacteria from the twins with MS to their healthy siblings, they found more than 50 types of bacteria (called microbial taxa) that were present in different amounts. One big finding was a noticeable increase in bacteria from a group called the Firmicutes phylum in the twins who had MS. Some of these specific bacteria had already been linked to MS in earlier studies, so this strengthens the idea that they might be involved in triggering or worsening the disease.
Going Deeper: Focusing on the Small Intestine
Most studies on gut bacteria usually analyze stool samples, which come from the large intestine. But this study took a different and more detailed approach. The researchers collected bacteria samples directly from various parts of the intestines, especially a specific area called the terminal ileum this is the last part of the small intestine, located just before the large intestine begins.
Why the terminal ileum? This part of the gut is known to be full of immune system activity, making it a key location where gut bacteria and immune cells closely interact. The researchers believed that certain bacteria living in this region might directly affect how immune cells behave, possibly in a way that could trigger the kind of immune response seen in MS.
By focusing on this area, the study aimed to find out if bacteria here have a stronger or more specific role in influencing the development of MS, compared to bacteria found in the lower parts of the gut
Transferring Human Gut Bacteria to Mice
To find out if the gut bacteria from people with MS could cause disease, the researchers did a special experiment. They took bacteria from the small intestine (specifically the terminal ileum) of the twins who had MS and put them into germ-free mice. These are special mice that are raised in a completely bacteria-free environment and have been genetically engineered to be more likely to develop a disease similar to MS, called EAE (Experimental Autoimmune Encephalomyelitis).
The results were surprising: mice that received bacteria from the MS-affected twins were much more likely to develop EAE compared to mice that received bacteria from the healthy twins. This strongly suggests that the gut microbes from people with MS can trigger disease in animals already genetically vulnerable to it.
Another important discovery: only the female mice got sick. This is especially interesting because MS is much more common in women than in men. So this part of the experiment not only supported the role of gut microbes in disease but also mirrored the gender pattern seen in human MS.
Key Bacteria Identified: The Lachnospiraceae Family
After studying the gut bacteria in the mice that got sick, the researchers were able to pinpoint two specific types of bacteria that seemed to play a big role: Eisenbergiella tayi and Lachnoclostridium. These bacteria belong to a larger group called the Lachnospiraceae family.
What’s interesting is that these bacteria are usually found in very small amounts in stool samples, so they had not received much attention in earlier studies. But in this study, they showed up clearly because the researchers sampled the small intestine, not just faeces.
In the mice that developed MS-like disease, these two species didn’t just appear they grew rapidly and took over large parts of the gut. Even more important, their presence was linked to changes in the immune system. Specifically, the mice had more inflammatory Th17 cells, which are a type of immune cell known to cause damage in MS. This suggests that these gut bacteria may be directly encouraging harmful immune activity that leads to the disease.
Why the Ileum Is Important
The small intestine, and especially a section called the ileum, plays a very important role in how the immune system learns to tell the difference between harmless and harmful substances. This part of the gut contains special immune structures called GALT (gut-associated lymphoid tissue). In this area, immune cells are constantly interacting with the bacteria and other microbes that live in the gut.
The researchers believe that the bacteria Eisenbergiella tayi and Lachnoclostridium may take advantage of this environment. These microbes could influence immune cells in the ileum in a harmful way, possibly by:
Molecular mimicry – this is when bacteria have molecules on their surface that look like parts of the body’s own cells. This can confuse the immune system and cause it to attack healthy tissue.
Inflammatory signalling – this means the bacteria might release substances that cause the immune system to become overactive or inflamed.
Either way, these interactions could activate T cells, a type of immune cell, and cause them to become autoimmune, meaning they start attacking the body’s nervous system, which is what happens in MS.
Why Females Were More Affected
One of the most interesting findings from the study was that only the female mice developed MS-like disease after receiving the gut bacteria from people with MS. This matches what we see in humans MS is about two to three times more common in women than in men.
The exact reason for this difference isn’t fully understood yet, but scientists think it may have to do with how female hormones or the female immune system interacts with certain bacteria. It’s possible that women’s bodies respond more strongly to gut bacteria that trigger inflammation, which could increase the chances of developing MS.
This part of the research highlights that sex differences may play a key role in how diseases like MS develop, especially when gut microbes are involved.
What This Could Mean for Future MS Treatments
If these findings are confirmed by more research, they could open the door to new ways of treating MS by focusing on the gut microbiome especially the harmful bacteria that may trigger the disease.
For example, future treatments might include:
Targeted probiotics (helpful bacteria) to crowd out the bad ones
Special antibiotics that remove only the harmful bacteria, like E. tayi and Lachnoclostridium
Diet changes that support a healthier gut and reduce inflammation
A New Approach to Understanding MS and Other Autoimmune Diseases
One important lesson from this study is the new method it used to analyze the gut bacteria. Instead of just looking at stool samples, which come from the large intestine, the researchers focused on bacteria taken directly from the small intestine. This is a big deal because it gives scientists a more detailed view of the gut microbiome and its role in diseases like MS.
This approach could be very helpful for studying other autoimmune diseases as well, not just MS. By analyzing the bacteria in different parts of the gut, researchers could get a better understanding of how these diseases develop and find more accurate ways to diagnose them. It might even lead to personalized treatments based on the unique microbiome of each patient.
Conclusion: A New Chapter in MS Research
This study marks a big step forward in understanding how gut bacteria might actually help cause multiple sclerosis (MS) not just be connected to it. By using a careful approach that included identical twin studies and germ-free mice experiments, the researchers were able to do more than just find suspicious bacteria. They showed that these microbes could trigger MS-like disease in the right conditions.
This research adds to the growing evidence of a strong link between the gut and the brain known as the gut–brain axis. As scientists continue to learn more about this connection, we may soon see new, safer, and more targeted treatments that work by adjusting gut bacteria. This could lead to better ways to prevent or manage autoimmune diseases like MS in the future.
References:
1.Altieri C, Speranza B, Corbo MR, Sinigaglia M, Bevilacqua A. Gut-Microbiota, and Multiple Sclerosis: Background, Evidence, and Perspectives. Nutrients. 2023 Feb 14;15(4):942. Doi: 10.3390/nu15040942. PMID: 36839299; PMCID: PMC9965298.
2. Hongsup Yoona, Lisa Ann Gerdesa , Florian Beigel et al, Multiple sclerosis and gut microbiota: Lachnospiraceae from the ileum of MS twins trigger MS-like disease in germfree transgenic mice—An unbiased functional study, PNAS 2025 Vol. 122 No. 18 e2419689122, https://doi.org/10.1073/pnas.2419689122
3. Thirion, F., Sellebjerg, F., Fan, Y. et al.The gut microbiota in multiple sclerosis varies with disease activity. Genome Med15, 1 (2023). https://doi.org/10.1186/s13073-022-01148-1
4. Vinod K. Gupta h Guneet S. Janda, Heather K. Pump Nikhil Lele et al, Alterations in Gut Microbiome-Host Relationships After Immune Perturbation in Patients With Multiple Sclerosis, Neurology: Neuroimmunology & Neuroinflammation | Volume 12, Number 2 | March 2025
5. Correale, J., Hohlfeld, R. & Baranzini, S.E. The role of the gut microbiota in multiple sclerosis. Nat Rev Neurol18, 544–558 (2022). https://doi.org/10.1038/s41582-022-00697-8
6. Hindson, J. A possible link between multiple sclerosis and gut microbiota. Nat Rev Neurol13, 705 (2017). https://doi.org/10.1038/nrneurol.2017.142
Add a Comment