Multiple sclerosis and gut microbiota: Lachnospiraceae from the ileum of MS twins trigger MS-like disease in germfree transgenic mice—An unbiased functional study

We developed a two-tiered strategy aiming to identify gut bacteria functionally linked to the development of multiple sclerosis (MS). First, we compared gut microbial profiles in a cohort of 81 monozygotic twins discordant for MS. This approach allowed to minimize confounding effects by genetic and early environmental factors and identified over 50 differently abundant taxa with the majority of increased taxa within the <i>Firmicutes</i>. These included taxa previously described to be associated with MS (<i>Anaerotruncus colihominis</i> and <i>Eisenbergiella tayi</i>), along with newly identified taxa, such as <i>Copromonas</i> and <i>Acutalibacter</i>. Second, we interrogated the intestinal habitat and functional impact of individual taxa on the development of MS-like disease. In an exploratory approach, we enteroscopically sampled microbiota from different gut segments of selected twin pairs and compared their compositional profiles. To assess their functional potential, samples were orally transferred into germfree transgenic mice prone to develop spontaneous MS-like experimental autoimmune encephalomyelitis (EAE) upon bacterial colonization. We found that MS-derived ileal microbiota induced EAE at substantially higher rates than analogous material from healthy twin donors. Furthermore, female mice were more susceptible to disease development than males. The likely active organisms were identified as <i>Eisenbergiella tayi</i> and <i>Lachnoclostridium,</i> members of the Lachnospiraceae family. Our results identify potentially disease-facilitating bacteria sampled from the ileum of MS affected twins. The experimental strategy may pave the way to functionally understand the role of gut microbiota in initiation of MS.