Bile acids have been suggested to be dysregulated in MS and have neuroprotective properties in vitro and in vivo. It is unknown whether serum levels of bile acid metabolites in early MS predict long-term disease progression.

In this prospective study, we measured primary and secondary bile acids in blood samples collected at baseline among the 468 participants in the BENEFIT clinical trial enrolled at the time of their clinically isolated syndrome. We used linear regression to examine the relationship of the bile acid metabolites with change in clinical disability (EDSS, MSFC) and radiological progression markers (T1-hypointense lesion volume, brain volume loss) to year 5. Bile acid concentrations were measured by liquid chromatography-mass spectrometry and were log transformed and standardized by sex. Models were adjusted for age, sex, initial treatment allocation, steroid treatment, multifocal symptoms, number of T2-lesions, and body mass index, and further for mean 25-hydroxyvitamin D and cigarette smoking as measured by repeated serum cotinine levels within the first 2 years from CIS. Investigations of other disease course markers and machine learning analyses are ongoing.

Higher levels of several primary and secondary bile acids were associated (p<0.05) with less deterioration in clinical disability as measured by EDSS (cholic acid, hyodeoxycholic acid) and MSFC (glycoursodeoxycholic acid, chenodeoxycholic acid glycine conjugate, lithocholic acid glycine conjugate). Bile acids were not associated with radiological progression markers. Adjusting the multivariable models further for vitamin D and smoking did not change the results.

Preliminary results of this metabolomic study suggest a bile acid dysregulation in early MS that may predict clinical MS progression 5 years after the first clinical episode.