Researchers find new correlations between the gut microbiota and immune response genes in people with multiple sclerosis

During the last 15 years, scientists have started to discover that the 100 trillion microorganisms living in our digestive tract –mostly in the colon- play a key role in different body functions, like digestion and training the immune system. What’s more, they have begun to learn that alterations in the gut microbiota are associated with an increased risk of diseases like obesity and diabetes, but also asthma, allergies, and even multiple sclerosis (MS).

In this vein, a new research study published in Nature Communications and led by investigators from Brigham and Women’s Hospital (BWH) found evidence that there is a connection between gut bacteria and MS. Investigators observed that people with multiple sclerosis have different patterns of gut microorganisms than those of their healthy counterparts.

And, importantly, they have also found that microbial changes in the gut correlated with changes in the activity of genes that play a role in the immune system.

“What we do not yet know is the direction of causality, that is if changes affect the risk or progression of MS. Further study will be needed to assess whether the changes we’ve observed play a role in, or are a consequence of, MS’s development”, recognizes Dr. Howard L Weiner, MD, director of the Partners MS Center and co-director of the Ann Romney Center for Neurologic Disease at Brigham Women’s Hospital, in an email interview with Gut Microbiota for Health.

The findings of this new research support recent studies linking immunological disorders to the gut microbiota and may have implications for pursuing new therapies for MS.

“Our findings raise the possibility that by affecting the gut microbiota one could come up with treatments for MS that affect the microbiota and in turn the immune response”, adds Weiner.

Multiple sclerosis (MS) is an incurable progressive disease that affects 2.3 million individuals worldwide. The disease involves the deterioration of the myelin sheathing covering the nerve cells in the brain and spinal column. As a consequence, patients feel numbness in limbs and suffer from speech deterioration, loss of muscle control, trouble with vision, and chronic fatigue. Although the cause is still not known, at least 200 genes have been identified as contributing to its development.

In the study, Weiner and colleagues sampled and analysed stool samples of 60 patients with MS and 43 healthy individuals from the control group. Researchers found two types of bacteria—Methanobrevibacter, the main methane-producing microbe in the human gut, and Akkermansia—were more abundant in MS patients. In contrast, those with MS had lower levels of others, such as Butyricimonas, in comparison with healthy individuals. The levels of microorganisms that differ in MS patients are thought to drive inflammation or have been associated with autoimmunity.

As investigators did not know whether the observed differences in gut microbiota composition could be due to medications given to MS patients, they split the initial samples into two groups: those treated with drugs and those not treated. They found the same results: both MS groups had elevated levels of the same two types of bacteria and a slight decline in Butirycimonas.

The team also collected breath samples from subjects, finding that as a result of increased levels of Methanobrevibacter, patients with MS had higher levels of methane in their breath samples, too.

All of these changes correlated with variations in the expression of immune response genes in blood immune cells, genes involved in cell maturation and signalling pathways.

“This work provides a window into how the gut can affect the immune system which can then affect the brain,” says Weiner, who is also a professor of Neurology at Harvard Medical School.

According to researchers, the next step will be to continue to explore the connection between the gut and the immune system in a larger group of patients and follow changes over time to better understand disease progression and interventions.

“Characterizing the gut microbiome could provide us with biomarkers for assessing disease activity and point us to new prevention strategies to help those who are at risk of developing the disease. We’re also interested in exploring how probiotics could be used to help reshape the gut microbiome in those are at risk,” concludes Weiner.

 

 

Reference

Sushrut Jangi, Roopali Gandhi, Laura M. Cox, et al. Alterations of the human gut microbiome in multiple sclerosisNature Communications, 2016; 7: 12015 DOI: 10.1038/NCOMMS12015