Gut microbiome in early pediatric multiple sclerosis: a case-control study (P4.027)

BACKGROUND/OBJECTIVE:Alterations in the gut microbiome may be influential in neurological disease. We explored gut microbiome profiles in early pediatric MS and age and sex matched controls. DESIGN/METHODS:Children ≤18 years old 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 onset. Controls were free from autoimmune disorders (asthma and eczema allowed). Stools were shipped on ice 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. RESULTS:Between Nov/2011-Nov/2013, 20 MS (10 girls, 10 boys) and 16 controls (9 girls, 7 boys) aged 13.2 years (mean; SD=3.84; range 4-18) provided stool samples. 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 12 to an immuno-modulatory or -suppressant drug (10 cases, 2 controls). All cases met McDonald criteria, had relapsing-remitting MS and a short disease duration (mean=11 months; range 2-24 at stool collection). The median EDSS at enrolment was 2.0 (range 0-4.0). Preliminary microbiome results indicated significant differences in specific bacterial taxa between cases and controls, with enriched tax predominated by Proteobacteria (e.g. Shigella, Escherichia), p<0.001, false discovery rates, q<0.192. Depleted taxa displayed greater heterogeneity, and included Firmicutes (Eubacterium rectale) and Actinobacteria (Corynebacterium) but also higher false discovery rates (all q<0.372 and p<0.044). CONCLUSIONS:Specific taxa were significantly altered in relative abundance in very early onset pediatric MS, with enrichment for microbiota known to be associated with gastrointestinal infectious processes. Study Supported by:NIH(NS071463);NMSS(RG4861A3/1);PI:Waubant