September 14, 2017 | News | MS Research

MS affected by ecology of the gut

Two new studies have shed more light on how the bacteria in the gastrointestinal tract can influence the progression of multiple sclerosis. The studies will be published later this week in the U.S. Proceedings of the National Academy of Sciences (Cekanaviciute and colleagues. PNAS 2017; in press).

Much of the body’s immune defences, designed to attack disease-causing organisms, are clustered at the points of entry, such as the gastrointestinal tract, nose, mouth and skin. In the gut (the stomach, small intestine and colon), immune cells are in constant communication with the micro-organisms living there (bacteria, viruses and fungi). Beneficial organisms are allowed to grow and develop, whereas harmful organisms trigger an immune response. It’s been estimated that the organisms living in the gut vastly outnumber the number of cells in the human body. This enclosed world has its own ecology – a complex interaction of different species living together. These organisms are collectively called the microbiome, a term that also refers to the collective genome (genetic code) of the gut inhabitants.

It’s now well-established that the microbiome will influence how our body’s immune system will respond. This raised the question of whether the microbiome could influence the dysfunctional immune response seen in MS. For example, some organisms could promote a more inflammatory response, which could cause the immune system to attack the body’s own tissues (an autoimmune response), while other organisms could reduce inflammation.

Indeed, some have suggested that the microbiome may be the most important environmental factor influencing the development and progression of MS.

In the current studies, researchers from the University of California-San Francisco compared the gut microbiome of 71 people with MS with 71 healthy people without MS. They found that the bacterial profile differed: there were several species of bacteria that were more or less common in people with MS.

In the second part of the experiment, the researchers took two strains of bacteria that were identified as more common in people with MS compared to healthy individuals, and exposed them to human immune cells. The bacteria triggered an inflammatory response. Then they repeated the experiment with a strain of bacteria that was more common in healthy individuals. Those bacteria triggered an immune-regulating response. The same thing happened when both experiments were repeated in mice: bacteria more commonly found in people with MS stimulated an inflammatory response, while bacteria more common in healthy people triggered a more regulated response.

What these findings mean is that the type of bacteria found in the gut can have a major impact on how the immune system responds. The gut bacteria in people with MS can contribute to the abnormal inflammatory reaction seen in MS. The immune system includes regulatory processes that can control inflammation. But people with MS appear to be lacking the type of bacteria that can stimulate the immune system to regulate itself. What remains to be determined is which is more important: triggering an inflammatory response, or lacking a regulatory response.

These findings are of theoretical interest, but they don’t address whether the immune responses in the gut have an impact on the immune response in the brain and spinal cord. For inflammation in the central nervous system is what matters in MS.

To address this question, the researchers completed additional experiments in mice with EAE (the experimental model of MS). They performed fecal transplants on the mice, in effect transferring the microbiome from people with MS to the animals. Fecal transplants were used because they wanted the experiment to reflect the complex ecology of the gut microbiome, rather than just the effect of one or two bacterial strains.

What they found was that following the fecal transfer, the mice lost key immune-regulating cells, which resulted in much more severe neurodegeneration. These findings suggested that the gut microbiome alone – independently of other genetic or environmental factors – had a major impact on the progression of disability. The further suggestion was that a lack of regulatory control – the hallmark of the autoimmune response – was a central problem to the development of inflammatory damage in MS.

The organisms in the gut aren’t believed to cause MS. But in genetically susceptible people, they may shift the tipping point so that the person develops MS, or has a worse long-term outcome.

Like all good research, these studies raise more questions than they answer. What are all the bacterial species that can affect MS? Would changing the types of bacteria in the gut (with probiotics, for example) make MS less severe, or enable the body to repair itself better? Are there dietary changes (or other treatments) that could change the ecology of the gut? Ongoing research at the University of California and other centres may provide some of the answers in the years ahead.

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