Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system (CNS) caused by genetic and environmental factors. This study focuses on a unique approach to gut bacteria by using monozygotic twins incompatible for the disease. Fecal samples were orally administered to germfree (GF) transgenic mice that are susceptible to spontaneous MS-like experimental autoimmune encephalomyelitis (EAE) following bacterial colonization.
Researchers found that ileal microbiota derived from MS-affected twins induced EAE more frequently than microbiota from their healthy cotwins. A receptor that recognizes the autoantigen myelin oligodendrocyte glycoprotein (MOG) on T cells is expressed by transgenic mice of the RR strain. When GF transgenic mice were colonized with intestinal microbiota from healthy SPF-bred mice and developed EAE, it indicates that intestinal microbiota is responsible for causing the disease.
Microbial taxa differentially prevalent in MS were identified by 16S rRNA sequencing of fecal samples from 81 monozygotic twin pairs. The study found 51 microbial species that show a difference between twins with MS and twins without MS using linear mixed models and a chi-squared test. Analysis of the luminal and mucosa-associated microbiota from the colon and ileum is possible by the enteroscopic sampling method from four pairs of twins. There were no noticeable variations in alpha or beta diversity between twins with MS and healthy twins.
The development of spontaneous EAE was common in mice colonized with the ileal microbiota of MS-Q than in mice inoculated with the microbiota of healthy cotwin HT-Q. Feces were stored at the endpoint and two weeks after colonization. Twelve weeks after colonization was completed or the onset of paralysis, the recipients were eliminated.
The study used a two-tailed unpaired t-test to compare two groups based on flow cytometry data, bacterial counts in feces, maximum EAE scores, and anti-MOG IgG levels. While Eisenbergiella tayi was found to be one of the organisms that were markedly elevated in MS twins, 16S rRNA sequencing is unable to resolve species at the level properly.
Enteroscopy was used to obtain microbiota samples from the colon and terminal ileum following standard bowel cleansing procedures. MS-Q had an EDSS of 6.0 at the time of this investigation, a 23-year disease duration, and an initially relapsing-remitting history of the disease that was associated with SPMS.
The central nervous systems (CNS) of mice colonized with ileal material from MS-Q but not from HT-Q exhibited inflammation and demyelinating lesions. Large population-based association studies demonstrate that changes in the gut microbial profile are associated with the likelihood of diagnosing MS. Using GF EAE-prone transgenic mice, this paradigm enables objective intestinal scanning for microorganisms that contribute to autoimmune diseases.
The high-level prevalence of EAE was observed in recipients of ileal samples from twin donors with MS. The small intestinal lamina propria activates CNS autoimmune CD4+ T cells, and these activated T cells then migrate into the CNS target region, as indicated by recent imaging investigations. The pathogenesis of MS will bridge the gap between microbial association and mechanical factors, incorporating site-specific sampling, functional microbiota testing, and strict genetic control.
Eisenbergiella tayi is a pathogen which result in anaerobic bloodstream infections for individuals with weak immunity. Thus it is important to learn more about Eisenbergiella tayi and their potential role in autoimmune conditions like MS. Explore the full pathogen profile here.
Reference: Yoon H, Gerdes LA, Beigel F, 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. Proc Natl Acad Sci U S A. 2025;122(18):e2419689122. doi:10.1073/pnas.2419689122
