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Multiple Sclerosis Linked to Gut Microbe Shift

NEW YORK (GenomeWeb) – The gut microbial communities of individuals with multiple sclerosis appear to be enriched for pro-inflammatory microbes such as Methanobrevibacter, according to a study published online today in Nature Communications.

Researchers from the University of Massachusetts and Harvard Medical School's Brigham and Women's Hospital did 16S ribosomal RNA sequencing on fecal samples from 60 individuals with MS and 43 unaffected controls to search for gut microbial components that differed in the cases.

The team considered these gut microbial patterns alongside results from blood and breath tests, which measured everything from blood gene expression and cytokine proliferation to methane concentration in the breath for dozens more cases and controls. The results pointed to a rise in Methanobrevibacter and Akkermansia species in the guts of treated and untreated patients — shifts corresponding to the extent of inflammatory signaling in patient blood samples.

"If further studies demonstrate that these candidate microorganisms play an active role in either contributing to or ameliorating MS, then there is the potential to develop new diagnostics and therapies to combat the disease," senior author Howard Weiner of the Partners Multiple Sclerosis Center at Brigham and Women's Hospital and his co-authors wrote.

The researchers used Roche 454 and Illumina MiSeq instruments to do 16S rRBA sequencing on DNA from fecal samples collected from 60 individuals with relapsing-remitting MS and 43 individuals without MS.

From the millions of reads generated with these short- and longer-read platforms, they identified more than 1,600 operational taxa units in the case and control samples.

Though the team did not see significant differences in beta diversity and overall structure of gut microbiomes in individuals with MS compared to those without, it did identify some bacterial phyla — particularly Euryarchaeota and Verrucomicrobia — that were over-represented in the gut microbial communities of cases.

To rule out gut microbiome changes caused by immunomodulatory treatment for MS, the researchers broke the case group down into 32 treated and 28 untreated patients, demonstrating that the phyla-level shifts in microbial abundance persisted — perhaps even to a slightly greater extent — in individuals without treatment.

Similarly, both treated and untreated patients showed a rise in representation by species from the Methanobrevibacter and Akkermansia genera, coupled with a decline in Butyricimonas bacteria. On the other hand, treated individuals tended to have higher levels of Prevotella and Sutterella bacteria in their guts, the team reported, but a dip in Sarcina bacteria relative to both untreated patients and controls.

To look at how these gut microbe patterns related to other clinical and biological features in the individuals with MS, the researchers went on to profile the expression of 568 immune-related genes in T-cell and monocyte immune cells in a subset of the cases and controls.

Reasoning that Methanobrevibacter, a microbe previously implicated in inflammation, was over-represented in cases in general, they focused on the 18 MS cases with the highest levels of Methanobrevibacter and the 18 controls with the lowest gut levels of that bug.

The available expression data was consistent with activation of interferon, NF-kappaB, and other inflammatory pathways in those immune cell types — shifts that were enhanced with increasing Methanobrevibacter or Akkermansia levels in the gut.

The team further explored potential contributions to MS features, using enzyme-linked immunosorbent assays to search for antibodies against Methanobrevibacter in blood samples from cases and controls and breath tests focused on methane produced by the bug.

If altered microbial community composition holds in future studies of MS, the study's authors argued that "treatment strategies of MS in the future may include therapeutic interventions designed to affect the microbiome." Moreover, they said, "characterization of the gut microbiome in MS may provide biomarkers for assessing disease activity and could theoretically be an avenue to prevent MS in young at-risk populations."