Gut microbiota function and relapse risk in pediatric multiple sclerosis (MS): using predictive metagenomics
ECTRIMS Online Library. Tremlett H. 10/25/17; 199326; EP1305
Helen Tremlett
Helen Tremlett
Contributions
Abstract

Abstract: EP1305

Type: ePoster

Abstract Category: Clinical aspects of MS - 3 Paediatric MS

Background: Previous work suggests a role for the gut microbiota in relation to relapse risk in paediatric MS. However, little is known about which microbial metabolic pathways might be involved.
Objective: To explore the association between the predicted relative abundances of gut microbial genes encoding metabolic and related pathways and relapse risk.
Methods: Children ≤18 years old attending a University of California, San Francisco pediatric MS clinic were invited to participate. All met McDonald criteria and were within 2 years of onset. Stools were shipped on ice and stored at -80C. The 16S ribosomal RNA gene was amplified from extracted DNA and sequenced via the Illumina MiSeq platform. Predicted function was assessed via the validated Phylogenetic Reconstruction of Unobserved States algorithm mapped to the Kyoto Encyclopedia of Genes and Genomes pathways. Longitudinal follow-up post-stool sample ('baseline') was obtained by mixed methods; both prospectively and through retrospective chart review. Assessors were unaware of the gut microbiota profiles. Associations between 11 a priori selected pathways (based on the wider literature and categorized as 'high vs. low' [≤ vs. > median] relative abundance of inferred microbial genes), were assessed in relation to subsequent relapse risk using survival analyses. Cox models were adjusted for age and disease-modifying drug (DMD) use.
Results: 17 relapsing-remitting MS cases (10 girls) aged 12.5 years (mean) with a mean disease duration of 10.3 months (range 2-23) provided stool samples. Eight (47%) were DMD naïve. Over a subsequent follow-up of up to 41.6 months (mean=19.8 months), 7 relapsed. A shorter time to relapse was associated with a lower relative abundance of microbial genes related to tryptophan metabolism (p=0.011, log-rank test) and higher abundances for both biotin metabolism and flavonoid biosynthesis (both p=0.018). After covariate adjustment for age and DMD exposure status, only flavonoid biosynthesis remained significant, although the 95% confidence intervals were wide (hazard ratio=20.3;95%CI:1.3-315.9, p=0.032).
Conclusions: Findings suggest that gut microbiota function may be associated with subsequent relapse risk. A high abundance of inferred microbial genes encoding flavonoid biosynthesis were associated with a shorter time to relapse relative to a child with low abundance. Further investigations are warranted.
Disclosure:
Helen Tremlett
is funded by the Canada Research Chair program and in the last year has received research support from the National Multiple Sclerosis Society, the Canadian Institutes of Health Research, the Multiple Sclerosis Society of Canada and the Multiple Sclerosis Scientific Research Foundation.
Douglas Fadrosh: nothing to disclose
Ali Faruqi: nothing to disclose
Janace Hart: nothing to disclose
Shelly Roalstad: nothing to disclose
Jennifer Graves is funded by the Race to Erase MS, Genentech, and the National MS Society
Susan Lynch is funded by the NIH, Sloan Foundation, Cystic Fibrosis Foundation, Broad Foundation, Jannsen Pharmaceuticals, Gilead and Pfizer.
Emmanuelle Waubant is funded by the NIH, the National MS Society, and the Race to Erase MS.
The US Network of Pediatric MS Centers (authors listed in alphabetical order): Greg Aaen1, Anita Belman2, Leslie Benson3, Charlie Casper4, Tanuja Chitnis3, Mark Gorman3, Yolanda Harris8, Lauren Krupp2, Tim E Lotze6, Sabeen Lulu7, Jayne Ness8, Cody Olsen4, Erik Roan4, Moses Rodriguez5, John Rose4, Timothy C Simmons4, Mendelt Tillema5, Wendy Weber4, Bianca Weinstock-Guttman9
1. Loma Linda University, Loma Linda, CA, United States; 2. Stony Brook University, Stony Brook, NY, United States; 3. Harvard University, Cambridge, MA, United States; 4. University of Utah, Salt Lake City, UT, United States; 5. Mayo Clinic, Rochester, MN, United States; 6. Baylor College of Medicine, Houston, TX, United States; 7. University of California, San Francisco, San Francisco, CA, United States; 8. University of Alabama, Birmingham, AL, United States; 9. State University of New York at Buffalo, Buffalo, NY, United States

Abstract: EP1305

Type: ePoster

Abstract Category: Clinical aspects of MS - 3 Paediatric MS

Background: Previous work suggests a role for the gut microbiota in relation to relapse risk in paediatric MS. However, little is known about which microbial metabolic pathways might be involved.
Objective: To explore the association between the predicted relative abundances of gut microbial genes encoding metabolic and related pathways and relapse risk.
Methods: Children ≤18 years old attending a University of California, San Francisco pediatric MS clinic were invited to participate. All met McDonald criteria and were within 2 years of onset. Stools were shipped on ice and stored at -80C. The 16S ribosomal RNA gene was amplified from extracted DNA and sequenced via the Illumina MiSeq platform. Predicted function was assessed via the validated Phylogenetic Reconstruction of Unobserved States algorithm mapped to the Kyoto Encyclopedia of Genes and Genomes pathways. Longitudinal follow-up post-stool sample ('baseline') was obtained by mixed methods; both prospectively and through retrospective chart review. Assessors were unaware of the gut microbiota profiles. Associations between 11 a priori selected pathways (based on the wider literature and categorized as 'high vs. low' [≤ vs. > median] relative abundance of inferred microbial genes), were assessed in relation to subsequent relapse risk using survival analyses. Cox models were adjusted for age and disease-modifying drug (DMD) use.
Results: 17 relapsing-remitting MS cases (10 girls) aged 12.5 years (mean) with a mean disease duration of 10.3 months (range 2-23) provided stool samples. Eight (47%) were DMD naïve. Over a subsequent follow-up of up to 41.6 months (mean=19.8 months), 7 relapsed. A shorter time to relapse was associated with a lower relative abundance of microbial genes related to tryptophan metabolism (p=0.011, log-rank test) and higher abundances for both biotin metabolism and flavonoid biosynthesis (both p=0.018). After covariate adjustment for age and DMD exposure status, only flavonoid biosynthesis remained significant, although the 95% confidence intervals were wide (hazard ratio=20.3;95%CI:1.3-315.9, p=0.032).
Conclusions: Findings suggest that gut microbiota function may be associated with subsequent relapse risk. A high abundance of inferred microbial genes encoding flavonoid biosynthesis were associated with a shorter time to relapse relative to a child with low abundance. Further investigations are warranted.
Disclosure:
Helen Tremlett
is funded by the Canada Research Chair program and in the last year has received research support from the National Multiple Sclerosis Society, the Canadian Institutes of Health Research, the Multiple Sclerosis Society of Canada and the Multiple Sclerosis Scientific Research Foundation.
Douglas Fadrosh: nothing to disclose
Ali Faruqi: nothing to disclose
Janace Hart: nothing to disclose
Shelly Roalstad: nothing to disclose
Jennifer Graves is funded by the Race to Erase MS, Genentech, and the National MS Society
Susan Lynch is funded by the NIH, Sloan Foundation, Cystic Fibrosis Foundation, Broad Foundation, Jannsen Pharmaceuticals, Gilead and Pfizer.
Emmanuelle Waubant is funded by the NIH, the National MS Society, and the Race to Erase MS.
The US Network of Pediatric MS Centers (authors listed in alphabetical order): Greg Aaen1, Anita Belman2, Leslie Benson3, Charlie Casper4, Tanuja Chitnis3, Mark Gorman3, Yolanda Harris8, Lauren Krupp2, Tim E Lotze6, Sabeen Lulu7, Jayne Ness8, Cody Olsen4, Erik Roan4, Moses Rodriguez5, John Rose4, Timothy C Simmons4, Mendelt Tillema5, Wendy Weber4, Bianca Weinstock-Guttman9
1. Loma Linda University, Loma Linda, CA, United States; 2. Stony Brook University, Stony Brook, NY, United States; 3. Harvard University, Cambridge, MA, United States; 4. University of Utah, Salt Lake City, UT, United States; 5. Mayo Clinic, Rochester, MN, United States; 6. Baylor College of Medicine, Houston, TX, United States; 7. University of California, San Francisco, San Francisco, CA, United States; 8. University of Alabama, Birmingham, AL, United States; 9. State University of New York at Buffalo, Buffalo, NY, United States

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