Bile acids as candidate therapies for multiple sclerosis: inverse signal analysis using the FDA adverse event reporting system and preclinical validation.

BACKGROUND

Alterations in bile acid metabolism have been observed in individuals with multiple sclerosis (MS), yet the therapeutic implications of bile acid supplementation remain uncertain.

METHODS

We conducted a two-stage study integrating pharmacovigilance analysis with preclinical validation to evaluate bile acid derivatives as candidate therapies for MS. A disproportionality analysis of the FDA Adverse Event Reporting System (FAERS; Q4/2003-Q2/2025) was performed to identify inverse associations between MS and bile acid preparations. The effects of ursodeoxycholic acid (UDCA) and obeticholic acid (6-ECDCA) were evaluated in a therapeutic experimental autoimmune encephalomyelitis (EAE) model, with treatment initiated after disease onset.

RESULTS

Among 13,734,539 FAERS reports, 75,659 involved MS. Inverse associations were identified for UDCA (odds ratio [OR]: 0.197, 95% confidence interval [CI]: 0.117-0.333) and 6-ECDCA (OR: 0.128, 95% CI: 0.041-0.396). In the EAE model, UDCA was associated with lower clinical scores at the peak (day 18) and late phases (days 26-28), whereas 6-ECDCA showed only a non-significant trend toward improvement at day 28.

CONCLUSION

This two-stage investigation highlights the potential utility of pharmacovigilance-guided approaches for identifying therapeutic candidates. Bile acid derivatives, particularly UDCA, are biologically plausible candidates meriting further investigation in the context of MS.