Acetate correlates with disability and immune response in multiple sclerosis

Silvia Pérez-Pérez; María Inmaculada Domínguez-Mozo; Aitana Alonso-Gómez; Silvia Medina; Noelia Villarrubia; Jose Ignacio Fernández-Velasco; María Ángel García-Martínez; Estefanía García-Calvo; Héctor Estévez; Lucienne Costa-Frossard; Jose C Alvarez-Cermeño; Jose L Luque-Garcia; Rafael Arroyo; Luisa M Villar; Roberto Alvarez-Lafuente

doi:10.7717/peerj.10220

Acetate correlates with disability and immune response in multiple sclerosis

PeerJ. 2020 Nov 16:8:e10220. doi: 10.7717/peerj.10220. eCollection 2020.

Authors

Silvia Pérez-Pérez^#¹, María Inmaculada Domínguez-Mozo^#¹, Aitana Alonso-Gómez¹, Silvia Medina², Noelia Villarrubia², Jose Ignacio Fernández-Velasco², María Ángel García-Martínez¹, Estefanía García-Calvo³, Héctor Estévez³, Lucienne Costa-Frossard⁴, Jose C Alvarez-Cermeño⁴, Jose L Luque-Garcia³, Rafael Arroyo⁵, Luisa M Villar², Roberto Alvarez-Lafuente¹

Affiliations

¹ Grupo de Investigación de Factores Ambientales en Enfermedades Degenerativas, Instituto de Investigación Sanitaria Hospital Clínico San Carlos (IdISSC) / Red Española de Esclerosis Múltiple (REEM), Madrid, Spain.
² Servicio de Inmunología, Hospital Universitario Ramón y Cajal. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) / Red Española de Esclerosis Múltiple (REEM), Madrid, Spain.
³ Department of Analytical Chemistry, Faculty of Chemical Sciences, Universidad Complutense de Madrid, Madrid, Spain.
⁴ Servicio de Neurología, Hospital Universitario Ramón y Cajal / Red Española de Esclerosis Múltiple (REEM), Madrid, Spain.
⁵ Department of Neurology, Hospital Universitario Quironsalud Madrid / Red Española de Esclerosis Múltiple (REEM), Madrid, Spain.

^# Contributed equally.

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.

Keywords: Acetate; EDSS; Multiple sclerosis; Plasma; Short chain fatty acids.

Grants and funding

Roberto Alvarez-Lafuente has a research contract from IdISSC. María Ángel García-Martínez has a technician contract from REEM (RD12/0032/0009). Silvia Pérez-Pérez has a research contract from MECD (FPU16/00969). This work was financially supported by ISCIII-Feder (PI15/00821), “Ministerio de Economía y Competitividad” (CTQ2017-85673-R), “Fundación Mutua Madrileña”, “Fundación Ramón Areces”, and “Fundación LAIR” grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.