Increased Archaea Species and Changes with Therapy in Gut Microbiome of Multiple Sclerosis Subjects (S24.001)

Abstract

OBJECTIVE: To determine if there are differences in the gut microbiome in MS and if changes occur with treatment. BACKGROUND: The gut microbiome plays a key role in shaping the immune repertoire and plays an important role in disease susceptibility in the EAE model. The gut microbiome has been described in other diseases but not yet in MS. DESIGNS/METHOD: MS patients from the Partners MS Center [untreated (n=22), glatiramer acetate treated (n=13), and IFN-b treated (n=18)] and healthy controls from the BWH PhenoGenetic project (n=44) were studied. Samples were profiled using two high throughput platforms (454 and Illumina 16s sequencing) to determine community structure and taxonomic composition of the gut microbome. RESULTS: We found an increase in Archaea (Methanobrevibacteriaceae) in MS vs. controls (p <0.00001 by 454 sequencing). Archaea are in a kingdom separate from bacteria and eukaryotes and in the human gut are dominated by Methanobrevibacter smithii, which make up 10% of colonic anaerobes in the gut. The cell wall and lipid membranes of M smithii make them strongly immunogenic consistent with a role in the induction of local and systemic inflammatory processes in the host. We also found two organisms with anti-inflammatory properties that were lower in MS vs. controls and which were increased with treatment. Specifically: 1) The Butyricimonas genus from Bacteroidetes phylum was lower in the untreated MS vs. controls. Butyricimonas are butyrate producers with anti-inflammatory effects; and 2) The Lachnospiraceae family from the Firmicutes phylum (which are also butyrate producers) was lower in untreated vs. treated MS irrespective of whether they were treated with IFN-β or glatiramer acetate. CONCLUSION: Our results identify changes in both pro-and anti-inflammatory epigenetic factors in the gut microbiome of MS subjects that may contribute to disease pathogenesis. Study supported by: NIH R21 and NMSS pilot grant.

Disclosure: Dr. Jhangi has nothing to disclose. Dr. Gandhi has nothing to disclose. Dr. Glanz has received research support from Merck Serono. Dr. Cook has nothing to disclose. Dr. Nejad has nothing to disclose. Dr. Ward has nothing to disclose. Dr. Li has nothing to disclose. Dr. Gerber has nothing to disclose. Dr. Bry has received personal compensation for activities as a consultant, scientific advisor, and speaker. Dr. Weiner has received personal compensation for activities with Biogen Idec, Novartis, EMD Serono, Teva Neuroscience, GlaxoSmithKline Inc., Nasvax, Xenoport Inc., and Genzyme Corp.. Dr. Weiner has received research support from Merck Serono.