# The gut microbiota composition is shaped by disease activity and individual treatment responses in patients with multiple sclerosis

## TL;DR

The gut microbiota in multiple sclerosis patients differs based on disease activity and treatment response, with non-responders showing signs of gut barrier dysfunction and inflammation.

## Contribution

This study reveals how gut microbiota composition is influenced by MS treatment outcomes and disease activity, linking microbial changes to immune system dysregulation.

## Key findings

- Patients with active disease or non-response to treatment showed reduced gut microbiota diversity and altered short-chain fatty acid-producing bacteria.
- Non-responders had elevated serum levels of lipopolysaccharide-binding protein and mannose-binding lectin, indicating compromised gut barrier function.
- Cladribine-treated patients showed distinct microbiota profiles regardless of treatment success, suggesting a strong influence of this therapy on gut composition.

## Abstract

Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system, with both animal and human studies highlighting a pivotal role for the gut microbiota in its pathogenesis. In this cross-sectional study, we investigated the potential role of gut microbiota in treatment response by analyzing its composition using 16S rRNA sequencing in treatment-naïve patients and those receiving disease-modifying therapies (interferon-beta (IFN-β), fingolimod, or cladribine), compared to healthy controls (HC). We also analyzed differences in gut microbiota composition and the serum levels of biomarkers associated with microbial translocation and inflammation based on treatment response. We found that individuals with clinically isolated syndrome (CIS) and treatment non-responders (NR) had significantly different alpha and beta diversity compared to HC. This effect was present in both IFN-β and fingolimod treatment. Individuals treated with cladribine had significantly different alpha and beta diversity regardless of the treatment outcome. The main differences in abundances in CIS and NR were found in bacteria that produce short-chain fatty acids. These patients also had significantly higher levels of lipopolysaccharide-binding protein and mannose-binding lectin compared to HC suggesting the compromised gut barrier function in multiple sclerosis leading to higher level of microbial translocation in these patients. In summary, we found that the treatment influences gut microbiota. Similar profile of gut microbiota and higher levels of molecules associated with microbial translocation were observed in patients with active disease (CIS and NR), suggesting the higher permeability of their gut barrier leading to pro-inflammatory tunning of their immune system.

Created with BioRender.com.Diagram illustrating therapy response in clinically isolated syndrome (CIS). It features a human figure receiving immunomodulatory treatments (Interferon-β, Fingolimod, Cladribine) and an analysis section detailing gut microbiota, serum SCFA levels, and inflammatory response. Key findings for non-responders include reduced alpha diversity, decreased SCFA-producing bacteria and serum SCFA, and impaired gut barrier function with elevated serum LBP and MBL levels. Brain images indicate therapy response outcomes.

Created with BioRender.com.