Acetate correlates with disability and immune response in multiple sclerosis

Silvia Pérez‐Pérez(Hospital Clínico San Carlos), María Inmaculada Domínguez‐Mozo(Hospital Clínico San Carlos), Aitana Alonso-Gómez(Hospital Clínico San Carlos), Silvia Medina(Spanish Multiple Sclerosis Network), Noelia Villarrubia(Spanish Multiple Sclerosis Network), José Ignacio Fernández-Velasco(Spanish Multiple Sclerosis Network), Maria Ángel García‐Martínez(Hospital Clínico San Carlos), Estefanía García‐Calvo(Universidad Complutense de Madrid), Héctor Estévez(Universidad Complutense de Madrid), Lucienne Costa‐Frossard(Spanish Multiple Sclerosis Network), José C. Álvarez‐Cermeño(Spanish Multiple Sclerosis Network), José L. Luque-García(Universidad Complutense de Madrid), Rafael Arroyo(Spanish Multiple Sclerosis Network), Luisa María Villar(Spanish Multiple Sclerosis Network), Roberto Álvarez‐Lafuente(Hospital Clínico San Carlos)
PeerJ
November 16, 2020
Cited by 40Open Access
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Abstract

Background Gut microbiota has been related to multiple sclerosis (MS) etiopathogenesis. Short-chain fatty acids (SCFA) are compounds derived from microbial metabolism that have a role in gut-brain axis. Objectives To analyse SCFA levels in plasma of MS patients and healthy donors (HD), and the possible link between these levels and both clinical data and immune cell populations. Methods Ninety-five MS patients and 54 HD were recruited. Patients were selected according to their score in the Expanded Disability Status Scale (EDSS) (49 EDSS ≤ 1.5, 46 EDSS ≥ 5.0). SCFA were studied in plasma samples by liquid chromatography-mass spectrometry. Peripheral blood mononuclear cells were studied by flow cytometry. Gender, age, treatments, EDSS and Multiple Sclerosis Severity Score (MSSS) were evaluated at the recruitment. Results Plasma acetate levels were higher in patients than in HD ( p = 0.003). Patients with EDSS ≥ 5.0 had higher acetate levels than those with EDSS≤ 1.5 ( p = 0.029), and HD ( p = 2.97e–4). Acetate levels correlated with EDSS ( r = 0.387; p = 1.08e–4) and MSSS ( r = 0.265; p = 0.011). In untreated MS patients, acetate levels correlated inversely with CD4+ naïve T cells ( r = − 0.550, p = 0.001) and directly with CD8+ IL-17+ cells ( r = 0.557; p = 0.001). Conclusions Plasma acetate levels are higher in MS patients than in HD. In MS there exists a correlation between plasma acetate levels, EDSS and increased IL-17+ T cells. Future studies will elucidate the role of SCFA in the disease.


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