Erngren Ida, Vaivade Aina, Carlsson Henrik, Al-Grety Asma, Åkerfeldt Torbjörn, Kockum Ingrid, Hedström Anna Karin, Alfredsson Lars, Olsson Tomas, Burman Joachim, Kultima Kim
Department of Medical Sciences, Clinical Chemistry, Uppsala University, Akademiska Sjukhuset, entrance 61, 3rd floor, Uppsala, 75185, Sweden.
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
BMC Med. 2025 Apr 9;23(1):212. doi: 10.1186/s12916-025-04041-x.
Bile acids (BAs) have emerged as important mediators in neuroinflammation and neurodegeneration, important features of multiple sclerosis (MS). This study aimed to examine serum BA levels in newly diagnosed people with MS (pwMS) and explore their association with disability worsening.
The study included 907 pwMS and 907 matched controls from the Swedish population-based EIMS cohort, with clinical follow-up data from the Swedish MS Registry. Serum BA levels were analyzed using liquid chromatography-high-resolution mass spectrometry. Differential expression analysis was used to study differences in BAs between pwMS and controls. Cox proportional-hazard models were used to assess associations between BA concentrations and confirmed disability worsening (CDW) and the risk of reaching EDSS milestones 4.0 and 6.0.
PwMS had lower concentrations of the primary conjugated BA, glycochenodeoxycholic acid (GCDCA, log FC - 0.29, p = 0.009) compared to controls. In relapsing-remitting MS compared to controls, lower concentrations of primary conjugated BAs (log2 FC - 0.30, p = 8.40E - 5), secondary conjugated BAs (log2 FC - 0.18, p = 0.007), and total BAs (log2 FC - 0.22, p = 2.99E - 4) were found. Sex-specific differences were also found, with male pwMS showing more substantial BA alterations. Elevated total BA levels were associated with increased risk for CDW (HR 1.22, 95% CI 1.08-1.39), driven mainly by primary conjugated (HR 1.19, 95% CI 1.06-1.33) and secondary conjugated BAs (HR 1.21, 95% CI 1.08-1.39).
This study identified alterations in serum BA profiles in pwMS compared to controls, with strong associations between conjugated BAs and the risk of disability worsening. These findings underscore the potential role of BAs in MS pathogenesis and disability worsening, suggesting they may be promising targets for future therapeutic interventions. Further research is warranted to clarify the underlying mechanisms of these associations.
胆汁酸（BAs）已成为神经炎症和神经退行性变的重要介质，而神经炎症和神经退行性变是多发性硬化症（MS）的重要特征。本研究旨在检测新诊断的MS患者（pwMS）的血清BA水平，并探讨其与残疾恶化的关系。
本研究纳入了来自瑞典基于人群的EIMS队列的907例pwMS患者和907例匹配对照，以及来自瑞典MS注册中心的临床随访数据。采用液相色谱-高分辨率质谱法分析血清BA水平。差异表达分析用于研究pwMS患者和对照之间BAs的差异。Cox比例风险模型用于评估BA浓度与确诊的残疾恶化（CDW）以及达到扩展残疾状态量表（EDSS）4.0和6.0里程碑风险之间的关联。
与对照相比，pwMS患者的初级结合型胆汁酸甘氨鹅脱氧胆酸（GCDCA，log FC -0.29，p = 0.009）浓度较低。与对照相比，复发缓解型MS患者的初级结合型胆汁酸（log2 FC -0.30，p = 8.40E -5）、次级结合型胆汁酸（log2 FC -0.18，p = 0.007）和总胆汁酸（log2 FC -0.22，p = 2.99E -4）浓度较低。还发现了性别特异性差异，男性pwMS患者的BA改变更为明显。总BA水平升高与CDW风险增加相关（风险比[HR] 1.22，95%置信区间[CI] 1.08 - 1.39），主要由初级结合型（HR 1.19，95% CI 1.06 - 1.33）和次级结合型胆汁酸（HR 1.21，95% CI 1.08 - 1.39）驱动。
本研究发现与对照相比，pwMS患者血清BA谱存在改变，结合型胆汁酸与残疾恶化风险之间存在密切关联。这些发现强调了胆汁酸在MS发病机制和残疾恶化中的潜在作用，表明它们可能是未来治疗干预有前景的靶点。有必要进一步研究以阐明这些关联的潜在机制。
