A recent study identified two potential microorganisms that differed in abundance between twins with and without multiple sclerosis symptoms that may be linked to the disease. These findings also suggest the role lifestyle habits play in the development of MS.

More than 280,000 people in Germany have MS and approximately 15,000 new cases are diagnosed each year. In MS, the body's own immune cells attack the insulating layer surrounding nerve fibers, damaging their function. Depending on where attacks occur, a wide variety of symptoms can arise.

Exactly how MS causes immune cells to become dysfunctional is still largely unclear. MS is a multifactorial disease — there is no single trigger, but rather several factors must come together for the disease to develop. In addition to genetic components, various environmental factors such as smoking, vitamin D deficiency, certain infectious diseases, and especially microorganisms in the gut have all been linked to the development of MS.

Previous studies have identified numerous bacterial strains that distinguish the intestinal flora of MS patients from that of healthy individuals. However, the significance of these differences for the course of the disease remained unclear. In addition, it was often difficult to interpret the results, as genetic differences or differing eating habits among the test subjects can have a major influence on the results.

Twin study provides clarity

To minimize these confounding factors, a team from several research institutions launched a major collaborative project — with the help of twins. Although identical twins share nearly the same genetic makeup, in some MS cases one twin may develop the disease while the other remains symptom-free — known as an MS-discordant pair.

Around 100 such twin pairs are currently taking part in the MS Twin Study at the Institute of Clinical Neuroimmunology at the University Hospital of the LMU Munich, enabling the disease to be studied under more comparable conditions. In addition to their minimal genetic differences, the twins lived together until early adulthood, meaning they were exposed to many of the same environmental factors.

Comparing the gut flora

The researchers examined stool samples from 81 pairs of twins enrolled in the study and compared their composition between siblings. They identified 51 taxa — groups of microorganisms — that differed in abundance between twins with and without MS symptoms.

In addition, the researchers went one step further in this study: Four of the twin pairs also agreed to have samples taken from their small intestines using enteroscopy. The disease-causing interactions between microorganisms and the body's own immune cells are believed to occur there. However, most previous studies have relied exclusively on stool samples, which provide only limited information about the microorganisms in the small intestine.

To test whether the samples from the small intestine contain disease-causing organisms, the researchers used special transgenic mice. These mice live a healthy life under germ-free conditions, however after colonization with gut bacteria, they can develop an MS-like disease. As part of the study, the mice were given samples from a twin with and without MS in parallel. Symptoms were mainly observed in mice that had been colonized with MS samples, indicating the presence of disease-causing microorganisms in the small intestines of people with MS.

The researchers then examined the feces of the diseased mice and identified two members of the Lachnospiraceae family (Lachnoclostridium and Eisenbergiella tayi) as potential disease-causing factors. Because of their low abundance in the intestine, these bacteria had previously only been linked to MS in large and well-controlled studies. However, the researchers were able for the first time to functionally characterize these bacteria and provide evidence for their pathogenicity.

The scientists emphasize there may be other microorganisms with the potential to trigger MS. Further studies are needed to obtain a more comprehensive picture and to examine the pathogenicity of the two candidates identified so far in detail — initially in a mouse model of the disease and later also regarding the transferability of the results to humans. However, if it turns out that only a small number of microorganisms trigger the disease, this could open up new therapeutic options. Strikingly, the study demonstrates the role lifestyle habits play in the development of MS and provides new experimental strategies to further investigate their effects.

The findings were published in the Proceedings of the National Academy of Sciences.