Americas Committee for Treatment and Research in Multiple Sclerosis
West Palm Beach, Florida


Gut Microbiome Offers Multiple Targets For Intervention in Progressive Multiple Sclerosis

Howard L. Weiner, MD, of Brigham and Women’s Hospital in Boston, presented data from his lab and other centers showing how gut microbiome approaches such as prebiotics, probiotics, and fecal microbiota transplant may influence outcomes in MS.WEST PALM BEACH, FL — Harvard University neurologist Howard Weiner, MD, has a gut feeling that altering the microbiome may have an impact on outcomes in multiple sclerosis (MS). Speaking at the ACTRIMS Forum on Saturday, February 29, Dr. Weiner presented data on microbiome strategies ranging from probiotic use to fecal transplant in animals and humans.

Dr. Weiner is the Robert L. Kroc Professor of Neurology at Harvard Medical School, Director and Founder of the Partners Multiple Sclerosis Center, and Co-Director of the Center for Neurologic Diseases at Brigham and Women’s Hospital in Boston, MA. Researchers in his lab have initiated a number of clinical trials exploring the influence of the gut microbiome in this disease. "I don't think there's any question that the microbiome plays a major role in not only neurological diseases, but other diseases as well," Dr. Weiner said. Studies of the gut flora in people with MS compared with healthy controls have found differences in levels of bacteria known to be harmful, as well bacteria now believed to be potentially helpful in MS.

In a recent microbiome study in MS, Dr. Weiner's team compared stool 16s rRNA samples from 41 healthy controls, 202 patients with relapsing MS (RMS), and 42 with progressive MS (PMS) to look for differences in alpha diversity, beta diversity, microbiome composition and associations with clinical parameters. "I think this is one of the first microbiome studies to look at things like EDSS and quality of life," he said. No differences were seen in alpha diversity (akin to the diversity of types of fish in the sea) although these differences have been shown in people with inflammatory bowel disease and obesity. "We are beginning to see some differences in beta diversity, and I think as we get larger cohorts, we'll be able to see them," Dr. Weiner reported.

Certain bacteria in the microbiome are beginning to emerge as good guys and bad guys in MS. Not surprisingly, those in the Clostridium family are bad guys. C. bolteae has been implicated in progressive MS. Akkermansia, once thought to be a bad influence, was shown to have beneficial correlations with EDSS in Dr. Weiner's study. MRI studies from other research groups have shown correlations with T2 lesion volume: beneficial for Akkermansia and detrimental for C. bolteae.

There are ways to therapeutically alter the microbiome, but exactly how to do that in people with MS remains unclear. Studies in Dr. Weiner's lab using a medical probiotic formulation showed immune system changes in monocyte gene expression, including increased IL-10 levels thought to be beneficial in MS. "It was interesting that after people came off the probiotic in the washout period, IL-10 levels remained elevated. This suggests there may be a way to modulate the immune system using probiotics," Dr. Weiner said. Other experimental approaches that appear promising include fecal microbiome transplant. Fecal stool transplant has been studied in animal models of MS, and human studies are beginning soon, Dr. Weiner said.

As far as definite conclusions about microbiome modulation in MS, we're not there yet, Dr. Weiner said. "I'm asked by my patients all the time, what should I take? What should I eat? What should I do?" he commented. "I have to obviously tell them we don't know yet. I advise them to follow a Mediterranean diet and don't eat a lot of potato chips or steaks."


By Katherine Wandersee, for the Consortium of Multiple Sclerosis Centers (CMSC)


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