Dominguez-Mozo Maria Inmaculada, López-Mecández Daniel, Villar Luisa María, Costa-Frossard Lucienne, Villarrubia Noelia, Aladro Yolanda, Pilo Belén, Montalbán Xavier, Comabella Manuel, Casanova-Peño Ignacio, González-Suárez Inés, Martínez-Ginés María Luisa, García-Domínguez Jose Manuel, García-Calvo Estefanía, Machuca-Marcos Andrés, Luque-Garcia Jose Luis, Garcia-Martinez María Angel, Arroyo Rafael, Alvarez-Lafuente Roberto
Grupo de Investigación de Factores ambientales en enfermedades degenerativas, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Red de Enfermedades Inflamatorias (REI), Red Española de Esclerosis Múltiple, Madrid, Spain.
Department of Clinical Analysis, Hospital Clínico San Carlos, Instituto de Medicina del Laboratorio (IML), Madrid, Spain.
Ann Clin Transl Neurol. 2025 Mar;12(3):478-490. doi: 10.1002/acn3.52259. Epub 2025 Mar 3.
An alteration in the composition of the intestinal microbiota has been observed in patients with multiple sclerosis (pwMS) with respect to healthy controls (HC). Microorganism-derived metabolites such as short-chain fatty acids (SCFA) have been suggested to play a role in the disease. Thus, to analyze the association of SCFA with clinical and radiological parameters of the disease and with those related to the inflammatory response of the immune system.
Multicentric observational retrospective cross-sectional study. In addition 161 pwMS and 130 HC were included. The following plasma SCFA were analyzed using liquid chromatography coupled to mass spectrometry: acetate (AA), propionate (PA) and butyrate (BA). Blood cell subpopulations and cytokine expression were analyzed by flow cytometry.
Plasma PA and PA/AA ratio was lower in pwMS than in HC (P = 0.0001, and P = 0.00005, respectively). PA/AA and BA/AA ratios were lower in pwMS with higher disability (P = 0.001, and P = 0.001, respectively). T2 lesion load inversely correlated with PA/AA (r = -0.353; P = 0.002) and BA/AA (r = -0.322; P = 0.005) ratios. Plasma PA/AA and/or BA/AA ratios negatively correlated with the following pro-inflammatory cytokines producing cells: GM-CSF+CD4+T, GM-CSF+CD8+T, TNF-alpha+CD4+T, TNF-alpha+CD8+T, IFN-gamma+CD4+T, IFN-gamma+CD8+T, and TNF-alpha+B cells.
In MS, plasma PA/AA and BA/AA ratios are unbalanced, promoting an environment that could be boosting the mechanisms underlying the pathogenesis of the disease. Since we have found statistical significant associations with the EDSS and the number of T2 lesions, but not with the number of relapses or gadolinium enhancing lesions, PA/AA and BA/AA ratios could be more associated with those mechanisms of the disease related to the neurodegenerative processes than those related with the activity of the disease.
与健康对照者（HC）相比，已观察到多发性硬化症患者（pwMS）的肠道微生物群组成发生改变。微生物衍生的代谢产物如短链脂肪酸（SCFA）被认为在该疾病中起作用。因此，分析SCFA与该疾病的临床和放射学参数以及与免疫系统炎症反应相关参数之间的关联。
多中心观察性回顾性横断面研究。此外，纳入了161例pwMS患者和130例HC。使用液相色谱-质谱联用分析以下血浆SCFA：乙酸盐（AA）、丙酸盐（PA）和丁酸盐（BA）。通过流式细胞术分析血细胞亚群和细胞因子表达。
pwMS患者的血浆PA和PA/AA比值低于HC（分别为P = 0.0001和P = 0.00005）。残疾程度较高的pwMS患者的PA/AA和BA/AA比值较低（分别为P = 0.001和P = 0.001）。T2病变负荷与PA/AA（r = -0.353；P = 0.002）和BA/AA（r = -0.322；P = 0.005）比值呈负相关。血浆PA/AA和/或BA/AA比值与以下促炎细胞因子产生细胞呈负相关：GM-CSF+CD4+T、GM-CSF+CD8+T、TNF-α+CD4+T、TNF-α+CD8+T、IFN-γ+CD4+T、IFN-γ+CD8+T和TNF-α+B细胞。
在MS中，血浆PA/AA和BA/AA比值失衡，促成了一种可能会促进该疾病发病机制的环境。由于我们发现与扩展残疾状态量表（EDSS）和T2病变数量存在统计学显著关联，但与复发次数或钆增强病变数量无关，因此PA/AA和BA/AA比值可能与该疾病中与神经退行性过程相关的机制比与疾病活动相关的机制更相关。
