It turns out the age-old saying, “you are what you eat,” might need a modern update: “you are what your gut bacteria eat (or don’t eat!).” New research suggests that the microscopic residents of our intestines, particularly in the small bowel, could play a starring role in the mysterious development of multiple sclerosis (MS).
For years, scientists have suspected a link between our gut microbes and MS, but pinpointing the exact culprits has been like finding a needle in a haystack. The challenge? Everyone’s gut microbiome—the unique community of bacteria, viruses, and fungi living in their digestive tract—is different, influenced by genetics, diet, lifestyle, and environment. This “noise” makes it incredibly difficult to isolate the true disease-causing factors.
Twins Offer a Unique Window into MS
To cut through this noise, researchers from the Munich MS Twin Study employed a clever, two-pronged approach. First, they leveraged their unique cohort of 81 pairs of identical twins where one twin has MS and the other doesn’t. This “discordant twin” design is a game-changer because it largely cancels out the confounding effects of genetics and early environmental factors, allowing the researchers to focus on the more subtle differences that might drive the disease. By analyzing stool samples from these twins, they identified over 50 different types of microbes that were present in different amounts between the MS-affected and healthy siblings. Many of these were from a group of bacteria called Firmicutes, and some had been previously linked to MS, like Anaerotruncus colihominis and Eisenbergiella tayi, while others were new discoveries, such as Copromonas and Acutalibacter.
Beyond Stool Samples: Exploring the Small Intestine
Identifying different bacteria isn’t enough; the key is to understand their function—whether they actively contribute to the disease. This led to the second, most innovative part of their strategy: functionally testing these microbes. While most studies rely on stool samples, which primarily reflect the gut’s “exit” point, the researchers hypothesized that the real action, where immune cells and bacteria interact to trigger MS, might be happening further up in the small intestine, specifically the ileum.
To test this, a small group of four twin pairs volunteered for a more invasive procedure: an enteroscopy. This allowed researchers to directly sample microbes from different parts of their intestines, including the terminal ileum and colon, as well as collect biopsies of the gut lining. This direct sampling provided a much clearer picture of the microbial communities living in these specific locations, showing how they differed from each other and from the stool samples.
Identifying the Likely Culprits
For the truly groundbreaking step, researchers brought these human microbes into a living system to see their effects. They used special germ-free mice—mice raised in a sterile environment, completely free of bacteria. These mice are also genetically predisposed to develop a spontaneous MS-like condition called experimental autoimmune encephalomyelitis (EAE) if they are colonized with certain bacteria. Essentially, they are a blank slate, ready to show how different microbial communities influence their immune system and disease development.
One female MS twin (MS-Q) and her healthy twin (HT-Q) were selected because MS-Q’s ileal microbial profile was notably different from her healthy sister’s. MS-Q had lived with MS for 23 years, initially with relapsing-remitting MS, but later transitioning to a more progressive form of the disease. Importantly, she hadn’t been on any disease-modifying treatment for over a decade when the samples were taken.
The researchers then took samples from the terminal ileum of MS-Q and transferred them into these germ-free mice. The results were striking: within 4 to 12 weeks, spontaneous EAE arose in three out of five recipient mice. Significantly, all the affected mice were female. This outcome is particularly relevant because MS is generally more prevalent and often more severe in women. In contrast, when mice were colonized with ileal microbiota from the healthy twin donor, EAE developed at substantially lower rates.
This experiment provided compelling functional evidence: the ileal microbiota from the MS-affected twin could trigger an MS-like disease in susceptible mice. But which specific bacteria were responsible? The researchers then carefully analyzed the feces of the diseased mice and identified two strong candidates: Eisenbergiella tayi and Lachnoclostridium, both members of the Lachnospiraceae family.
These bacteria had been previously identified in large studies as being more abundant in individuals with MS, but their low numbers in the gut made it difficult to prove their direct involvement. This new study, however, provided the first functional evidence of their disease-causing potential, at least in a mouse model. While the scientists emphasize that other microorganisms may also contribute to MS, and more research is needed to fully understand their role and how these findings translate to humans, this study provides a powerful new direction. As the researchers stated, “If it turns out that only a small number of microorganisms trigger the disease, this could open up new therapeutic options.”
This research highlights the profound impact of our gut microbiome on our health, suggesting that the tiny organisms living within us may be orchestrating critical aspects of autoimmune diseases like MS.
Paper Summary
Methodology
The study used a two-part approach: comparing gut bacteria in fecal samples from 81 pairs of identical twins where one had MS and the other didn’t, and then functionally testing gut microbes from four twin pairs. For the functional test, researchers directly sampled bacteria from the small intestine of selected twins and transferred them into germ-free mice prone to an MS-like condition. This allowed them to see which bacteria might trigger the disease.
Results
In the twin study, 51 types of bacteria were found to be different between MS-affected and healthy twins, mostly from the Firmicutes group, including some new discoveries. Crucially, when gut bacteria from an MS-affected twin were given to germ-free mice, 3 out of 5 female mice developed an MS-like disease. This was much higher than in mice given bacteria from a healthy twin. The specific bacteria identified as likely triggers were Eisenbergiella tayi and Lachnoclostridium, both from the Lachnospiraceae family.
Limitations
The study’s initial analysis of twin fecal samples had limited statistical power due to its size. The more in-depth study involving direct gut sampling and mouse experiments included only four twin pairs, which is a very small group. The findings from the mouse model may not directly apply to humans, and the method used to identify bacteria (16S rRNA sequencing) couldn’t always pinpoint the exact species. Researchers also noted that other microorganisms might also play a role in MS.
Funding and Disclosures
The authors reported no conflicts of interest. The article is open access under the Creative Commons Attribution License 4.0 (CC BY). Several authors contributed equally to the work.
Publication Information
Yoon, H., Gerdes, L. A., Beigel, F., Sun, Y., Kövilein, J., Wang, J., Kuhlmann, T., Flierl-Hecht, A., Haller, D., Hohlfeld, R., Baranzini, S. E., Wekerle, H., & Peters, A. (2025). Multiple sclerosis and gut microbiota: Lachnospiraceae from the ileum of MS twins trigger MS-like disease in germfree transgenic mice—An unbiased functional study. Proceedings of the National Academy of Sciences, 122(18), e2419689122. Published April 21, 2025.