|Gut microbiome in early pediatric multiple sclerosis: a case-control study|| |
|H Tremlett1, D Fadrosh2, S Lynch2, J Hart2, J Graves2, S Lulu2, G Aaen3, A Belman4, L Benson5, C Casper6, T Chitnis5, M Gorman5, L Krupp4, TE Lotze7, J Ness8, S Roalstad6, M Rodgriguez9, J Rose6, J-M Tillema9, B Weinstock-Guttman10, E Waubant2, US Network of Pediatric MS Centers|
|1University of British Columbia, Vancouver, BC, Canada, 2University of California, San Francisco, CA, United States, 3Loma Linda University, Loma Linda, CA, United States, 4Stony Brook University, Stony Brook, NY, United States, 5Harvard University, Cambridge, MA, United States, 6University of Utah, Salt Lake City, UT, United States, 7Baylor College of Medicine, Houston, TX, United States, 8University of Alabama, Birmingham, AL, United States, 9Mayo Clinic, Rochester, MN, United States, 10State University of New York at Buffalo, Buffalo, NY, United States|
|Background: Alterations in the gut microbiome may be influential in neurological disease.|
Objectives: We explored gut microbiome profiles in early pediatric MS and age and sex matched controls.
Methods: Children aged 18 years or under attending a University of California, San Francisco pediatric clinic were invited to participate in a genetic and environmental risk factors study (NS071463, PI Waubant). MS cases were within 2 years of symptom onset. Controls were free from autoimmune disorders (asthma and eczema allowed), with neither parent affected by MS or related disorders. The child's first stool of the day was shipped on ice to the laboratory and stored at -80C. The 16S rRNA gene was amplified from extracted DNA and bacterial profiles were generated using the PhyloChip G3 microarray (Second Genome, Inc., CA). Associations between the pediatric characteristics and variation in the bacterial community composition were assessed using nonmetric multidimensional scaling and permutational multivariate analysis of variance with distance matrices (Adonis function in the vegan R package).
Results: Between Nov/2011-Nov/2013, 20 MS (10 girls, 10 boys) and 16 controls (9 girls, 7 boys) provided stool samples for microbiome analysis. The mean age at collection was 13.2 years (SD=3.84; range 4-18) and 19/36 (14 cases, 5 controls) identified as non-white. Within two months pre-stool collection, 3 children (2 cases, 1 control) were exposed to an antibiotic, 10 (8 cases, 2 controls) to a corticosteroid and within three months, 12 to an immuno-modulatory or -suppressant drug (10 cases,
2 controls). For cases, the mean disease duration at stool collection was 11 months (range 2-24), the median EDSS at enrollment was 2.0 (range 0-4.0); all met McDonald criteria and had relapsing-remitting MS. Preliminary microbiome results indicated significant differences in community composition between cases and controls, with enrichment of Proteobacteria (Shigella, Escherichia) and Firmicutes (Clostridium) and depletion of Firmicutes (Eubacterium rectale) and Actinobacteria (Corynebacterium) observed in MS (all p< 0.01; false discovery rate, q< 0.217). Additional data analyses will be completed by Aug/2014.
Conclusions: Preliminary findings indicate that in very early pediatric MS, gut microbiome composition is significantly altered, with enrichment for microbiota known to be associated with gastrointestinal infectious processes.
Helen Tremlett , University of British Columbia , Vancouver , CA
Assigned in sessions:
12.09.2014, 14:45-16:15, Poster viewing, poster sessions, P2, Poster Session 2 (P491-P981) and Coffee Break, Hall C