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The gut microbiome of patients with multiple sclerosis appears to be altered in characteristic ways that may inform future therapeutic approaches.

Although multiple sclerosis (MS) is a chronic disease that affects the brain and spinal cord, it has been hypothesized that a disrupted bacterial and viral gut microbiota contributes to the pathogenesis of the disease. This study, published in Genome Medicine, provides an analysis of this relationship as it functions through the altered gut microbiotaโ€“brain axis. The aim of the study was to explore the association between gut microbiota in MS and various disease variables to better understand its etiology.ย 

Data from 148 individuals with MS, along with 148 matching controls were used. Shotgun sequencing of fecal microbial DNA was performed and bacterial and viral microbiota findings were associated with plasma cytokines, blood cell gene expression profiles, and disease activity.ย 

Gut Microbiome Findings in Patients with MS Versus Healthy Controls

When MS cases were compared with healthy controls 61 differentially abundant bacterial species were found, 31 of which were enriched in cases. A group of inflammation markers composed of blood leukocytes, CRP, and blood cell gene expression of IL-17A and IL-6 was associated with a cluster of MS-related species. A link was also found between bacterial species that were more prominent in disease-active treatment-naive MS cases and plasma cytokines, including IL-22, IL-17A, IFN-ฮฒ, IL-33, and TNF-ฮฑ.ย 

In non-disease-active cases, two bacterial species were identified: Faecalibacterium prausnitzii and Gordonibacter urolithinfaciens. These bacteria have been shown to produce anti-inflammatory metabolites such as butyrate and urolithin. Cases with MS showed higher viral species diversity, and an increased rate of Caudovirales bacteriophages.

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MS Patients Show Unique Changes in Microbiota

Significant aberrations were found in the gut microbiota of patients with MS, and these were directly linked with blood biomarkers of inflammation. In treatment-naive cases, bacterial richness was positively associated with disease activity, providing further context for these results. The two symbiotic bacterial species that were found in non-disease-active cases provide a rationale for testing these bacteria as adjunct therapeutics in future clinical trials due to their production of immune-modulating compounds.ย 

Some limitations of the study include the lack of fecal and plasma metabolomics, which are useful for directly measuring differences in bacterial metabolites. Gut mycobiome data would have also been useful to get a full picture of gut microbiota, as it has recently been reported to be altered in MS patients.

Source:

Thirion, F., Sellebjerg, F., Fan, Y., Lyu, L., Hansen, T. H., Pons, N., Levenez, F., Quinquis, B., Stankevic, E., Sรธndergaard, H. B., Dantoft, T. M., Poulsen, C. S., Forslund, S. K., Vestergaard, H., Hansen, T., Brix, S., Oturai, A., Sรธrensen, P. S., Ehrlich, S. D., & Pedersen, O. (2023). The gut microbiota in multiple sclerosis varies with disease activity. Genome Med, 15(1), 1. https://doi.org/10.1186/s13073-022-01148-1