Systematic review identifies consistencies and gaps in MS microbiome studies

There is growing evidence across a range of neurological disorders that the gut microbiome has a relationship with inflammation and changes in the brain. The bugs in your gut are beneficial for health including brain health, through—for example—production of beneficial metabolites and regulation of the immune system. Studies have shown differences in the microbial composition in people with diseases and healthy controls, but what are those differences, and how much do we know about what those bacteria are doing for people with multiple sclerosis (MS)?

Dr. Helen Tremlett has been looking at the link between the gut microbiome and MS for the past four years. A new systematic review from Dr. Tremlett and MS Society of Canada-funded PhD candidate Ali Mirza, published recently in the journal Multiple Sclerosis and Related Disorders, has found some consistent associations with specific microbes across existing literature, cleared gaps in terms of what research has been done and what questions we still need to ask about the gut-brain connection.

“The relationship between the gut microbiome and neurological diseases, such as MS, is an exciting but still emerging area of interest,” explained Dr. Tremlett. “We wanted to see what had been published and if findings were consistent across the existing MS literature.”

What they found offered perspective on the current state of gut microbiome research.

“As of 2018, across the ten published studies we identified on MS and the gut microbiota, fewer than 300 people with MS—and 300 healthy controls—had been included, which shows how limited current knowledge is,” said Dr. Tremlett.

However, the team were also encouraged by the results, with consistency in findings observed across several studies. While the overall diversity of the gut microbiota was generally similar between people with MS and people without, at the individual microbe level, interesting differences emerged.

“We found six distinct groups of bacteria consistent across several studies, with several either higher or lower in people with MS,” said Mirza, a student in UBC’s Bioinformatics Graduate Program. “What was encouraging is that we saw some consistency in findings, even when there were differences in research methods.”

“In people with MS, studies observed lower relative abundance of some key microbes, but higher relative abundance of other microbes such as Akkermansia,” said Dr. Tremlett. “You can see similar findings in other neurological diseases, but interestingly, a lower relative abundance of Akkermansia might actually be beneficial in some conditions such as obesity or metabolic disease. Clearly a lot more work needs to be done to understand what it means for people living with MS.”

These findings build on Dr. Tremlett’s existing research, and will inform the direction of a longer-term microbiome collaboration. A 2016 study by Dr. Tremlett and frequent collaborator Dr. Emmanuelle Waubant at the University of California-San Francisco found that children with MS show a difference in the relative abundance of groups of microbes as early as two years into the disease course; that same year, the researchers found a relationship between a reduced relative abundance of Fusobacteria in the gut and increased risk of relapse.

“What will be important going forward is to understand if there are confounding factors affecting the gut microbiome in people with MS,” said Dr. Tremlett. “For example, what is the role of disease-modifying drugs and other medications in altering the gut microbial community in people with MS? Do other co-existing conditions such as constipation or depression have an effect, and how best to consider dietary factors? There is much we still don’t know. I am optimistic and excited about what we will learn in the next few years and ultimately hope that findings can be used to benefit people with MS.”

The study authors received funding from The Multiple Sclerosis Scientific and Research Foundation, EGID: 2636 (PI: Tremlett). Ali Mirza was supported by an endMS Doctoral Studentship Award from the Multiple Sclerosis Society of Canada, EGID: 3246.