Pauline Anderson

May 02, 2014

PHILDELPHIA — Researchers are making some intriguing discoveries about the gut of patients with multiple sclerosis (MS).

One new study has identified both pro- and anti-inflammatory epigenetic factors in the intestinal microbiome of patients with MS that may contribute to disease pathogenesis.

"We have assembled a cohort of patients from whom we can compare gut microbial signatures, immunologic and clinical characteristics," Sushrut Jhangi, MD, an internal medicine specialist in Boston, Massachusetts, told delegates.

Their new findings were presented here at the American Academy of Neurology (AAN) 66th Annual Meeting.

Gut Microbiome

For this new study, researchers collected fecal samples from 168 patients with MS and 43 healthy control patients. Samples were profiled using 2 high-throughput platforms (454 and Illumina 16s sequencing) to determine community structure and taxonomic composition of the gut microbiome, the ecological community of microorganisms in the body.

The study excluded patients who had recently used antibiotics or probiotics, recently had gastroenteritis, or had a history of inflammatory bowel disease, rheumatoid arthritis, or bowel surgery.

The mean age of the patients with MS was 44.8 years compared with 38.7 years in the control patients; 29% of the patients with MS were men compared with 18.6% of the control patients. The mean body mass index in the MS group was 27.3 kg/m2; it was 26.2 kg/m2 in the control group. In the MS group, 85.2% were white, whereas 100% of the control group was white.

The mean disease duration in the MS group was 11.4 years, and the mean Expanded Disability Status Scale score was 1.2. This group included only those with relapsing-remitting MS, 44 of whom were untreated and 49 who were taking some type of interferon.

There were no significant differences in dietary patterns between patients with MS and control patients. About 13% of the MS and 24% of the control groups had a history of vegetarian dieting, 52% of both groups had high milk consumption, and 67% of the MS and 48% of control groups had a high level of yogurt consumption.

The study found that alpha diversity and beta diversity were comparable between the patients with MS and healthy control patients. However, there were differences between the 2 groups at the genus or species level; specifically, patients with MS were highly enriched for archaea (P < .00001 by 454 sequencing in MS vs controls), regardless of treatment.

Archaea are 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.

Inflammatory Processes

Dr. Jhangi explained that the cell wall and lipid membranes of M smithii make them strongly immunogenic, which is consistent with a role in the induction of local and systemic inflammatory processes in the host.

The study found that patients with MS who were highly enriched for Methanobrevibacter had significantly increased Expanded Disability Status Scale scores (1.85 vs 1.1; P = .036) and a trend toward longer disease duration (15.7 vs 12.5 years; P = .19) compared with patients with MS who were poorly enriched.

The researchers also found 2 organisms with anti-inflammatory properties that were lower in MS vs control patients and that increased with treatment.

Dr. Jhangi outlined differences in gut microbes associated with other autoimmune diseases. For example, patients with new-onset rheumatoid arthritis are enriched for Prevotella copri, and in inflammatory bowel disease, butyrate producers are depleted.

Among the next research steps for Dr. Jhangi and colleagues is to do repeat sequencing in a larger cohort (they now have 250 patients) and to carry out further fecal analysis, methane breath testing, and whole-genome sequencing.

"Really Fascinating"

Asked for her opinion of this new study, Lily Jung Hensen, MD, a neurologist at Swedish Neurosciences Institute, Seattle, Washington, said it was "really fascinating," because it may help the medical profession understand how an environmental component may have an effect on MS causation.

As well, she said, "further down the road," such research could potentially allow for the manipulation of MS therapeutics.

Dr. Jung Hensen said she anticipates that her patients with MS, after hearing of this new connection between the disease and gut flora, will be keen to know all about what is in their own intestines.

However, she added, "Obviously, we need to reproduce these findings, so a lot more work needs to be done before we have anything that is actionable."

The study was supported by grants from the National Institutes of Health and the National Multiple Sclerosis Society.

American Academy of Neurology (AAN) 66th Annual Meeting: Abstract S24.001. Presented Wednesday April 30, 2014.

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