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bas, pubmed, acid, article, pwms, bile, google, scholar, disability, analysis, worsening, edss, risk, conjugated, multiple, disease, sclerosis, study, table, data, concentrations, cdw, serum, cas, differences, central, metabolism, sex, acids, included, found, levels, primary, significant, swedish, reaching, smoking, receptor, spr, association, secondary, gut, observed, additional, log, increased, controls, associations, lower, compared,

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supplementary information 12916_2025_4041_moesm1_esm author information authors springer nature additional information publisher discussion sharing state privacy rights including abbreviations cox proportional-hazard models abbreviations ad rights ethics committee confirmed disability worsening high-resolution hybrid quadrupole information lars alfredsson & tomas olsson sphingosine-1-phosphate receptor 2 central nervous system cox regression results serum bile acids content jb acknowledges funding kk acknowledges funding secondary bile acids methods cohort av acknowledges funding conjugated bile acids author correspondence original author cross-sectional karmen study relapsing–remitting ms compared privacy choices/manage cookies increased gut-barrier permeability conclusions large case–control study bile salt hydrolase healthy adults–results bile acids association neurofilament light chain sample collection acknowledges funding bile acid precursors differential expression analysis national population registry process typically mediated treat multiple sclerosis progressive multiple sclerosis stratified results based nature cns autoimmunity observed

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         headline:Bile acid metabolism in multiple sclerosis is perturbed and associated with the risk of confirmed disability worsening
         description: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, log2 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.
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      name:The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Centrum for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
      name:Academic Specialist Center, Stockholm, Sweden
      name:Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
      name:Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
      name:Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
      name:Centre for Occupational and Environmental Medicine, Stockholm, Sweden
      name:Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
      name:The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Centrum for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
      name:Academic Specialist Center, Stockholm, Sweden
      name:Department of Medical Sciences, Translational Neurology, Uppsala University, Uppsala, Sweden
      name:Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden

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