|Gut microbiome is linked to immune cell phenotype in multiple sclerosis|| |
|R Gandhi1, FV Glehn1, MA Mazzola1, S Jangi1, B Glanz1, S Cook1, P Nejad1, J Petrosino2, D Ward3, N Li1, GK Gerber1, L Bry1, H Weiner1|
|1Brigham and Women's Hospital, Boston, MA, United States, 2Baylor College of Medicine, Houston, TX, United States, 3Broad Institute, Cambridge, MA, United States|
|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.|
Objectives: To determine if there are differences in the gut microbiome in MS and if gut microbiome could be linked to immune cell phenotype in MS.
Methods: MS patients from the Partners MS Center [untreated (n=22), glatiramer acetate treated (n=13), and IFN- 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. The gut microbiome was also linked to immune cell profiling in peripheral blood using flow based and nanostring based assays.
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. 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. Immune cell analysis showed that the antigen presenting cells from MS patients have an activated phenotype that could be linked to presence or absence of Archaea. In addition, we found that the expression of T cell specific markers such as IFN-gamma, a proinflammatory cytokine associated with MS, is also linked to the presence or absence of Archaea.
Conclusions: 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 and that could be linked to changes in immune cell phenotype.
Assistant Professor Roopali Gandhi , Brigham and Women's Hospital , Boston , US
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