Dataset Information

Bile acid metabolites predict multiple sclerosis progression and supplementation is safe in progressive disease.

ABSTRACT:

Background

Bile acid metabolism is altered in multiple sclerosis (MS) and tauroursodeoxycholic acid (TUDCA) supplementation ameliorated disease in mouse models of MS.

Methods

Global metabolomics was performed in an observational cohort of people with MS followed by pathway analysis to examine relationships between baseline metabolite levels and subsequent brain and retinal atrophy. A double-blind, placebo-controlled trial, was completed in people with progressive MS (PMS), randomized to receive either TUDCA (2g daily) or placebo for 16 weeks. Participants were followed with serial clinical and laboratory assessments. Primary outcomes were safety and tolerability of TUDCA, and exploratory outcomes included changes in clinical, laboratory and gut microbiome parameters.

Results

In the observational cohort, higher primary bile acid levels at baseline predicted slower whole brain, brain substructure and specific retinal layer atrophy. In the clinical trial, 47 participants were included in our analyses (21 in placebo arm, 26 in TUDCA arm). Adverse events did not significantly differ between arms (p=0.77). The TUDCA arm demonstrated increased serum levels of multiple bile acids. No significant differences were noted in clinical or fluid biomarker outcomes. Central memory CD4+ and Th1/17 cells decreased, while CD4+ naïve cells increased in the TUDCA arm compared to placebo. Changes in the composition and function of gut microbiota were also noted in the TUDCA arm compared to placebo.

Conclusion

Bile acid metabolism in MS is linked with brain and retinal atrophy. TUDCA supplementation in PMS is safe, tolerable and has measurable biological effects that warrant further evaluation in larger trials with a longer treatment duration.

SUBMITTER: Ladakis DC

PROVIDER: S-EPMC10827276 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

Bile acid metabolites predict multiple sclerosis progression and supplementation is safe in progressive disease.

Ladakis Dimitrios C DC Harrison Kimystian L KL Smith Matthew D MD Solem Krista K Gadani Sachin S Jank Larissa L Hwang Soonmyung S Farhadi Farzaneh F Dewey Blake E BE Fitzgerald Kathryn C KC Sotirchos Elias S ES Saidha Shiv S Calabresi Peter A PA Bhargava Pavan P

medRxiv : the preprint server for health sciences 20240123

<h4>Background</h4>Bile acid metabolism is altered in multiple sclerosis (MS) and tauroursodeoxycholic acid (TUDCA) supplementation ameliorated disease in mouse models of MS.<h4>Methods</h4>Global metabolomics was performed in an observational cohort of people with MS followed by pathway analysis to examine relationships between baseline metabolite levels and subsequent brain and retinal atrophy. A double-blind, placebo-controlled trial, was completed in people with progressive MS (PMS), randomi ...[more]

PMID: 38293182

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Dataset Information

Bile acid metabolites predict multiple sclerosis progression and supplementation is safe in progressive disease.

Background

Methods

Results

Conclusion

Publications

Bile acid metabolites predict multiple sclerosis progression and supplementation is safe in progressive disease.

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