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

Patients with clinically isolated syndrome (CIS) and treatment non-responders (NR) had significantly different alpha and beta diversity compared to healthy controls.

• Alpha and beta diversity differences were observed in both CIS patients and treatment non-responders (NR) relative to healthy controls (HC).
• This pattern was present across multiple treatment groups including IFN-β and fingolimod.
• The study used 16S rRNA sequencing to analyze gut microbiota composition.
• The cross-sectional design compared treatment-naïve patients and those on disease-modifying therapies to HC.

Patients treated with cladribine had significantly different alpha and beta diversity regardless of treatment outcome.

• Unlike IFN-β and fingolimod groups where diversity differences were linked to treatment response, cladribine-treated individuals showed diversity differences irrespective of whether they were responders or non-responders.
• This suggests cladribine has a distinct effect on gut microbiota composition compared to other disease-modifying therapies.
• Gut microbiota was analyzed using 16S rRNA sequencing.

The main differences in bacterial abundances in CIS and non-responders involved bacteria that produce short-chain fatty acids.

• Short-chain fatty acid (SCFA)-producing bacteria were identified as the primary taxa differing between active disease groups (CIS and NR) and healthy controls.
• Differences in SCFA-producing bacteria were shared between CIS patients and treatment non-responders, suggesting a common microbiota profile in active disease.
• Short-chain fatty acids are known to play roles in immune regulation and gut barrier integrity.

CIS patients and treatment non-responders had significantly higher serum levels of lipopolysaccharide-binding protein (LBP) and mannose-binding lectin (MBL) compared to healthy controls.

• Elevated LBP and MBL levels suggest compromised gut barrier function in patients with active MS disease.
• Higher levels of these molecules are interpreted as evidence of increased microbial translocation in CIS and NR patients.
• LBP and MBL are biomarkers associated with microbial translocation and inflammation.
• Serum biomarker levels were analyzed alongside gut microbiota composition in the same cohort.

Active MS disease (CIS and treatment non-response) is associated with a pro-inflammatory immune tuning linked to gut barrier permeability.

• Similar profiles of gut microbiota and higher levels of microbial translocation markers were observed in both CIS patients and treatment non-responders.
• The authors conclude this shared profile reflects 'higher permeability of their gut barrier leading to pro-inflammatory tuning of their immune system.'
• This finding connects gut barrier dysfunction to disease activity and treatment failure in MS.
• The study included treatment-naïve patients (CIS) and patients on IFN-β, fingolimod, or cladribine, stratified by treatment response.

Disease-modifying treatment influences gut microbiota composition in MS patients.

• The study compared gut microbiota across treatment groups: treatment-naïve (CIS), IFN-β, fingolimod, and cladribine, relative to healthy controls.
• Different treatments were associated with distinct microbiota profiles, with cladribine showing the most pronounced effect independent of treatment response.
• Both IFN-β and fingolimod treatment groups showed microbiota differences that were associated with treatment response status.
• 16S rRNA sequencing was used for microbiota characterization in this cross-sectional study.