OBJECTIVE: To determine if there are differences in the gut microbiome in multiple sclerosis and if changes occur with treatment.
BACKGROUND: The gut microbiome plays a key role in shaping theimmune 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
BACKGROUND: The gut microbiome plays a key role in shaping theimmune 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
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