Alteration of bile acid profile in patients with neuromyelitis optica spectrum disorders and multiple sclerosis

OBJECTIVE: Despite increasing evidence of the interaction between bile acid (BA) metabolism and immune regulation, the role of BAs in neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) remains unclear.

METHODS: Plasma concentrations of 24 BAs were quantified using targeted metabolomics in 40 NMOSD patients, 35 MS patients, and 41 healthy controls (HCs) during both relapse and remission phases. Clinical correlations with disability and imaging findings were also analyzed.

RESULTS: During relapses, NMOSD patients exhibited significantly lower 5-cholenic acid-3β-ol levels (6.53 ± 2.83 nM) compared to MS patients (9.00 ± 3.48 nM, p < 0.001) and HCs (8.78 ± 2.93 nM, p < 0.001). Glycohyocholic acid (GHCA) levels were elevated in NMOSD (48.65 ± 59.17 nM, p < 0.001) and MS (63.80 ± 101.24 nM, p = 0.001) compared to HCs (11.04 ± 12.54 nM). Glycohyodeoxycholic acid (GHDCA) levels were higher in MS patients (2.88 ± 3.18 nM) than in HCs (1.03 ± 0.84 nM, p = 0.002). In NMOSD, 5-cholenic acid-3β-ol negatively correlated with extended disability status scale scores (γ s = -0.631, p < 0.001) and spinal cord lesion length (γ s = -0.376, p = 0.017). During remission, levels of 5-cholenic acid-3β-ol, GHCA, and GHDCA normalized in NMOSD and MS patients.

CONCLUSION: These findings reveal distinct BA alterations in NMOSD and MS, highlighting 5-cholenic acid-3β-ol as a promising biomarker for disease differentiation and activity monitoring in NMOSD.