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Boston—The gastrointestinal tract may seem like an odd place to look for insight into a neurologic disease, but a small study has identified an association between two types of bacteria found in the gut and the development of multiple sclerosis.

The work is the first in humans to map the microbiome in patients with MS, and may provide clues to causes of some cases, according to the researchers. Changes in the gut microbiome have been linked to other autoimmune disorders, including inflammatory bowel disease and rheumatoid arthritis (Inflamm Bowel Dis 2006;12:106-111; Curr Opin Rheumatol 2014;26:410-415), said Sushrut Jangi, MD, an instructor in medicine at Harvard Medical School, in Boston, who led the latest study.

“MS has more in common with inflammatory bowel disease, rheumatoid arthritis, lupus and some of the other immune diseases than neurodegenerative diseases,” Dr. Jangi said. “In all of those autoimmune diseases, the immune system is attacking its own tissues because it has been activated by some bacteria, virus or environmental trigger. We don’t know what causes MS, and one thought is that there is a bacteria in your body that may predispose you or contribute to you getting MS. The gut has more bacteria than any other part of the body, so it makes sense to look there.”

In the new study, the investigators obtained fecal samples from 61 patients with MS and 43 healthy people. The study included untreated MS patients (n=19) as well as those treated with interferon β-1a (n=21), interferon β-1b (n=2), glatiramer acetate (n=18) and natalizumab (n=1).
The researchers performed genetic sequencing on the samples to determine the specific microbial taxa of all study participants. The two cohorts had similar baseline characteristics in terms of factors that are known to influence gut bacteria, such as body mass index.

The investigators found that the average abundance of Methanobrevibacter was seven times greater in patients with MS than in the control group, but not every MS patient had the bacteria.Methanobrevibacter has been increasingly linked to multiple inflammatory states, but its ability to drive immune responses is not well understood, according to Dr. Jangi.

Methanobrevibacter also live in the healthy gut, but they seem to be increased in MS patients,” he said. “Is that because in MS, the gut is not working that well that it lets theMethanobrevibacter grow more readily or is the bug somehow associated with causing the disease? It is a chicken-and-egg problem.”

The investigators also found that the average abundance of Butyricimonas was three times lower in untreated patients with MS than in healthy controls. But the levels of Butyricimonas in treated patients and healthy controls did not differ significantly, suggesting that treatment has an effect on this bacteria.
The possible role of Butyricimonas in the immune system is better understood. 

WhenButyricimonas digests dietary fiber, butyrate is produced. Butyrate influences the production of regulatory T cells in the gut (Nature 2013;504:446-450). Previous studies have shown that patients with autoimmune conditions such as type 1 diabetes and inflammatory bowel disease have lower levels of butyrate-producing bacteria (Rev Diabet Stud 2012;9:251-259; Nestle Nutr Inst Workshop Ser 2014;79:29-39). “Butyrate probably helps to dampen the immune response,” Dr. Jangi said.
Emeran Mayer, MD, director of the Center for Neurobiology of Stress, in the Division of Digestive Diseases at the University of California, Los Angeles, said the findings were interesting.

“I think the study is important as alterations in the gut microbiome have previously been implicated in the pathophysiology of MS,” Dr. Mayer said. “However, even though conceivable that an altered gut microbial state may play some role in fully developed MS, the observed microbial differences could be a consequence of the disease—altered neurovisceral regulation of GI [gastrointestinal] transit, secretion or the stress associated with the disease—or it could be related in some way to the altered function of the immune system in autoimmune disorders.”

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