Gut Bacteria, Diet Significant in Multiple Sclerosis

NASHVILLE, Tennessee — People with multiple sclerosis (MS) show differences in gut bacteria composition compared with those without the disease, new research shows.

In a separate report presented here at the Consortium of Multiple Sclerosis Centers (CMSC) 2018 Annual Meeting, patients with MS best adhering to a Mediterranean-style diet showed improvements in mood and cognition.

The findings add to increasing interest in potentially key roles of gut microbiota and dietary metabolites in MS, researchers say.

"There are statistically significant differences in the microbiome composition of MS patients versus healthy donors," report the authors of the former study. "Statistically significant differences are also found in patients with stable versus active disease."

Important evidence from animal models has shown that gut microbiota can potentially drive immune-mediated demyelination, suggesting a role of the microbiome in MS pathogenesis.

To further investigate the issue in humans, the researchers evaluated 42 stool samples from patients who had relapsing-remitting MS or secondary progressive MS with relapses and compared them with samples from 28 healthy donors.

They found that samples from patients with relapsing-remitting MS had significantly higher abundance of Ruminococcus torques, Ruminococcus obeum, and Lactospiraces bacterium compared with healthy controls, which were confirmed at the genus level (P < .01).

Escherichia coli and Oscillibacter had the second strongest association in the MS group (P ≤ .02), confirmed at the genus and family levels.

Bacteria that were more abundant in healthy controls compared to patients with relapsing-remitting MS included Bacteroides fragilis and Roseburia (P < .01); Haemophilus parainfluenzae and Sutterella wadsworthensis were also in higher abundance in healthy controls at the species, genus, and family levels (P < .05).

S wadsworthensis was also significantly higher in patients with MS with stable disease (P < .01).

Eubacterium ramulus was in significantly higher abundance in patients with active MS (P < .03), confirmed at genus and family levels, and Bacteroides finegoldii and Ruminococcus lactaris were also significantly higher in patients with MS with active disease (P < .02).

"We think the most significant findings are that Sutterella and Haemophilus parainfluenzae were in higher levels in healthy controls compared to the MS patients, and Sutterella was also significantly higher in stable versus active MS patients, so the findings were consistent in both analyses," coauthor Daniela Pimentel Maldonado, MD, from the Department of Neurology at the University of Massachusetts Medical School, Worcester, told Medscape Medical News.

"Other larger studies have also shown these bacteria to be present in healthy controls and stable patients, so we have essentially been able to reproduce those other studies," she said.

Maldonado noted that more research is needed to consider important issues, such as the many possible factors that could explain some of the differences, including use of antibiotics, diet during a relapse, and even levels of exercise.

"In further research, we want to look at antibiotic use and questions such as whether patients have more urinary tract infections, which could prompt them to take more antibiotics and could change their gut microbiome," she said.

The team is continuing to collect stool samples to get more longitudinal data on changes in patients' gut microbiome.

"There is a lot more we need to understand," Maldonado said. 'We know the gut microbiome is important, but we don't know what is driving the changes, or if patients should take probiotics or if there are other factors that could be influencing this, so it's going to be exciting to look at these issues."

"Mobilizing" the Gut Microbiome

Addressing the issue of gut microbiota in a separate talk at the CMSC meeting, Ilana Katz Sand, MD, from the Corinne Goldsmith Dickinson Center for MS at the Icahn School of Medicine at Mount Sinai, New York City, underscored the increasing interest in the bacterial composition of the gut and how it relates to MS.

"We know that 70% of the body's immune system is housed inside the gut and there are very important communications between the immune system in the gut and the peripheral immune system, as well as direct communication between the gut and the central nervous system," she said.

"So, this is a very important area of research and it makes sense to ask why shouldn't we be trying to mobilize what our body already has in order to try to promote tolerance?"

Dietary metabolites can have direct effects on immune tolerance in the gut, through mechanisms such as G-protein–coupled receptors, which are expressed on intestinal epithelial cells as well as on immune cells, she explained.

In investigating the potential effects of diet in MS, Sand and her team are conducting a clinical trial looking at possible benefits of the Mediterranean-style diet in patients with MS. This diet is rich in vegetables, fruits, nuts, seafood, and polyunsaturated fat; is low in red and processed meats and refined sugars; and features moderate alcohol consumption.

While results have not been published yet, Sand said the effects of diet on disease may be much more significant than many realize.

"Many people are looking at the feasibility and potential for symptom management (with diet changes), but I think we need to be looking at their potential as disease modifiers," she said.

Mediterranean Diet Affects Depression, Cognition?

Results from another small but intriguing study presented at the meeting suggest that mood modification may be added to the various potential benefits of a Mediterranean-style diet.

The diet has been associated with improvements in the general population in measures of mood, fatigue, and cognitive impairment — all issues that factor significantly in MS.

In the study of 34 patients with MS, researchers asked participants to report on their adherence to a Mediterranean-style diet in a 24-hour dietary recall.

Participants self-reporting higher adherence to a Mediterranean-style diet had significantly less severe symptoms for depression (P = .01) and cognitive impairment (P = .02), as measured on Neuro-Quality of Life subscales.

In addition, those in the highest tertile of scores for adherence to the Mediterranean diet had significantly lower depressive symptoms than those in the lowest tertile (mean difference, 4.1; 95% confidence interval, 0.17 - 8.03).

No association was seen with the Mediterranean diet scores and measures of fatigue.

"Our findings suggest that the Mediterranean diet is potentially related to depression and cognitive function in people with MS," first author Leah Mische, BS, from the Johns Hopkins University School of Medicine, Baltimore, Maryland, told Medscape Medical News.

Limitations, in addition to the study's size, include the lack of adjustment for the degree of disability. Mische noted that it's difficult to know whether the diet has a causative role or whether there is an opposite effect, for instance whether factors such as depression and cognitive impairment could, understandably, worsen a person's diet.

However, the findings help expand on potential benefits of the Mediterranean diet in diseases beyond cardiovascular disease.

"This type of study has not been done before in terms of looking at the relationship with MS," Mische said. "Right now, much of our understanding of the Mediterranean diet comes back to this issue of cardiovascular disease risk. However, some of that can also translate to MS because we know that having comorbid cardiovascular disease is associated with worse outcomes in almost every feature of MS."

"Larger, longitudinal studies as well as well-designed randomized controlled trials are needed, but hopefully this provides some motivation for doing that, knowing there is this association between neuropsychiatric comorbidity and MS with the Mediterranean diet."

The authors have disclosed no relevant financial relationships.

Consortium of Multiple Sclerosis Centers (CMSC) 2018 Annual Meeting. Abstracts NP04 and NN10. Presented June 1, 2018.

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