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. 2024 Nov 15:18:349-361.
doi: 10.2147/BTT.S489523. eCollection 2024.

Short and Medium Chain Fatty Acids in a Cohort of Naïve Multiple Sclerosis Patients: Pre- and Post-Interferon Beta Treatment Assessment

Laura Barcutean  1   2 , Lenard Farczadi  3 , Ion-Bogdan Manescu  4 , Silvia Imre  3   5 , Smaranda Maier  1   2 , Rodica Balasa  1   2
Affiliations

Short and Medium Chain Fatty Acids in a Cohort of Naïve Multiple Sclerosis Patients: Pre- and Post-Interferon Beta Treatment Assessment

Laura Barcutean et al. Biologics. .

Abstract

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.

Keywords: acetic acid; butyric acid; caproic acid; cytokine; gut microbiota; matrix metalloproteinase; propionic acid.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Boxplot type diagrams with median and 95% CI showing comparison analysis of baseline SCFAs/MCFA levels and after one year of IFNβ treatment (all p>0.05).
Figure 2
Figure 2
Boxplot type diagrams with median and 95% CI. Comparisons between MMP9, AA, PA, BA and CA between nMS and HC (**** extremely high significance, ** moderate significance).
Figure 3
Figure 3
Heatmap displaying correlations between SCFA, MMP9, and IL-10. Each cell represents the correlation coefficient with colors indicating the strength and direction of correlation. The statistically significant correlations are marked with *. (Spearman’s rho).
Figure 4
Figure 4
Correlations between PA and BA, CA and IL-10, MMP9 and IL-10, MMP9 and AA (Scatter Plot, Spearman’s Rho).
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