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

Abstract

Laura Barcutean,1,2 Lenard Farczadi,3 Ion-Bogdan Manescu,4 Silvia Imre,3,5 Smaranda Maier,1,2 Rodica Balasa1,2 1Department of Neurology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Targu Mures, 540142, Romania; 2Neurology 1 Clinic, Mures County Emergency Clinical Hospital, Targu Mures, Romania; 3Chromatography and Mass Spectrometry Laboratory, Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Targu Mures, Mures, 540139, Romania; 4Department of Laboratory Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Targu Mures, 540142, Romania; 5Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Targu Mures, 540142, RomaniaCorrespondence: Lenard Farczadi, Chromatography and Mass Spectrometry Laboratory, Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Targu Mures, Mures, 540139, Romania, Email [email protected]: 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: butyric acid, propionic acid, acetic acid, caproic acid, cytokine, gut microbiota, matrix metalloproteinase

Keywords

• butyric acid
• propionic acid
• acetic acid
• caproic acid
• gut microbiota
• matrix metalloproteinase.