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Short and Medium Chain Fatty Acids in a Cohort of Naïve Multiple Sclerosis Patients: Pre- and Post-Interferon Beta
Laura Barcutean1,2, Lenard Farczadi3, Ion-Bogdan Manescu4
1Department of Neurology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Targu Mures, 540142, Romania.
Introduction:
Alterations in intestinal permeability and microbiota dysregulation have been linked to the development of multiple sclerosis (MS). Short-chain fatty acids (SCFA) and medium-chain fatty acids (MCFA) are products of gut bacteria fermentation which are involved in immune regulation processes. In MS, SCFA have important immunomodulatory properties both in the periphery and the central compartment. Interferon β (IFNβ) was the first disease-modifying therapy approved for the treatment of MS and its effects on the gut microbiota are not fully elucidated.
Patients And Methods:
We performed a prospective observational study aimed to assess peripheral levels of SCFA and MCFA in 23 newly diagnosed, treatment-naïve MS patients (nMS) before and after one year of IFNβ treatment and 23 healthy controls (HC). We investigated their associations with inflammation, interleukin-10 (IL-10), and blood-brain barrier permeability, matrix metalloproteinase 9 (MMP9).
Results:
No significant differences in SCFA/MCFA levels were observed between baseline and after IFNβ treatment. Caproic acid levels were significantly higher in nMS compared to HC (1.64 vs 1.27 µM, p=0.005). The butyric acid/caproic acid ratio was higher in HC compared to nMS (5.47 vs 2.55, p=0.005). Correlation analysis revealed associations between SCFA/MCFA levels and inflammatory biomarkers.
Conclusion:
nMS have a higher gut-inflammatory activity as seen by the caproic acid ratio as opposed to HC. In this cohort, IFNβ does not appear to modify the peripheral SCFA/MCFA levels after one year of treatment. The quantifications of peripheral SCFA/MCFA may prove to be a useful biomarker for gut-brain axis disruption in MS patients.
Insights
Multiple sclerosis patients show altered gut bacteria metabolites, specifically higher caproic acid. Interferon beta treatment did not change these levels after one year, suggesting SCFA/MCFA may indicate gut-brain axis disruption in MS.
Area of Science:
- Neuroimmunology
- Microbiome research
- Metabolomics
Background:
- Gut microbiota dysregulation and intestinal permeability are implicated in multiple sclerosis (MS) pathogenesis.
- Short-chain fatty acids (SCFA) and medium-chain fatty acids (MCFA) are microbial metabolites with crucial roles in immune regulation.
- The impact of Interferon beta (IFNβ), a primary MS therapy, on gut microbial metabolites remains unclear.
Purpose of the Study:
- To investigate peripheral SCFA and MCFA levels in newly diagnosed, treatment-naïve MS patients compared to healthy controls.
- To assess the effect of one-year IFNβ treatment on these metabolite levels in MS patients.
- To explore associations between SCFA/MCFA levels and inflammatory/neuromyelitis markers.
Main Methods:
- Prospective observational study design.
- Recruitment of 23 treatment-naïve MS patients and 23 healthy controls.
- Measurement of peripheral SCFA and MCFA levels pre- and post-one year of IFNβ treatment.
Main Results:
- No significant changes in overall SCFA/MCFA levels were observed after IFNβ treatment.
- MS patients exhibited significantly higher caproic acid levels compared to healthy controls.
- A higher butyric acid/caproic acid ratio was found in healthy controls versus MS patients.
- Correlations were identified between SCFA/MCFA levels and key inflammatory biomarkers.
Conclusions:
- Newly diagnosed MS patients display altered peripheral SCFA/MCFA profiles, indicative of increased gut-inflammatory activity.
- IFNβ therapy did not significantly alter peripheral SCFA/MCFA levels after one year in this cohort.
- Peripheral SCFA/MCFA quantification may serve as a valuable biomarker for gut-brain axis dysfunction in MS.
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