Abstract Details

Title Serum and Stool Metabolites Are Associated with Transition from Relapsing-remitting to Progressive Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) P8 - Poster Session 8 (5:30 PM-6:30 PM)

Poster/Presentation
Number 6-012

Objective

To investigate whether patients who transition from relapsing-remitting to progressive multiple sclerosis (MS) have alterations in serum and stool metabolites. Identifying patients who transition to progressive MS is crucial for understanding the biology of progressive MS.

Background

Patients with secondary progressive MS (SPMS) have altered microbiota compared to patients with relapsing-remitting (RRMS) disease and controls (HC). Gut microbiota can influence the host through numerous means, including microbially derived metabolites with immunomodulatory capacity.

Design/Methods We performed liquid chromatography with tandem mass spectrometry (LC-MS/MS) for global metabolic profiling of serum and stool from 23 HC, 23 stable RRMS, 21 SPMS, and 21 RRMS who transitioned to SPMS at 2-year follow-up (RRMS->SPMS). ANCOVA was used to detect differences in metabolite levels between groups while adjusting for covariates.

Results Greater than 1000 metabolites were identified, of which 264 in serum and 132 in stool were different across disease status. SPMS and RRMSàSPMS shared similar metabolic profiles in stool and blood vs. HC. Palmitoleate was increased in patients with a relapse, associated with higher EDSS, and also elevated in SPMS and RRMS->SPMS compared to HC. Several microbially-derived metabolites including secondary bile acids were significantly decreased in SPMS and RRMS->SPMS, but not in RMS compared to HC, including ursodeoxycholate and isoursodeoxycholate.

Conclusions

RRMS subjects who transition to SPMS have serum and stool metabolic alterations similar to SPMS. Secondary bile acids are potential beneficial metabolites which have shown efficacy in mouse models of MS and were reduced in SPMS and RRMS->SPMS in our study. This approach may identify both microbial mediators of disease progression and novel therapeutic targets to treat MS.

Authors/Disclosures
Federico Montini (Mayo Clinic College of Medicine and Science) PRESENTER	Mr. Montini has nothing to disclose.
Luke Schwerdtfeger, PhD (Brigham and Women's Hospital)	Dr. Schwerdtfeger has nothing to disclose.
Bonnie Glanz (Brigham and Women'S Hospital)	The institution of Ms. Glanz has received research support from CMSC. The institution of Ms. Glanz has received research support from NIH.
Tanuja Chitnis, MD, FAAN (Brigham and Women's Hospital)	Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Chitnis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche-Genentech. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octave Biosciences. Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. The institution of Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Chitnis has received research support from Novartis. The institution of Dr. Chitnis has received research support from Sanofi. The institution of Dr. Chitnis has received research support from Octave. The institution of Dr. Chitnis has received research support from Genentech-Roche. The institution of Dr. Chitnis has received research support from Tiziana Life Sciences. The institution of Dr. Chitnis has received research support from Bristol-Myers Squibb. The institution of Dr. Chitnis has received research support from Wesley Clover.
Laura M. Cox (Harvard Medical School)	Dr. Cox has received personal compensation for serving as an employee of Anaerobe Systems.
Howard L. Weiner, MD (Brigham and Women'S Hospital)	Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tiziana Life Sciences. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for vTv Therapeutics. Dr. Weiner has stock in vTv Therapeutics. The institution of Dr. Weiner has received research support from National Institute of Health. The institution of Dr. Weiner has received research support from National MS Society. The institution of Dr. Weiner has received research support from Genzyme Corp. The institution of Dr. Weiner has received research support from Genentech, Inc. . The institution of Dr. Weiner has received research support from Verily Life Sciences LLC. The institution of Dr. Weiner has received research support from EMD Serono, Inc..

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