Multiple Sclerosis Society of Canada

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New collaborative study funded by the MS Scientific Research Foundation will explore how the microbes in the gut influence MS in children and adolescents

  • Canadian Study
  • MS Society Funded

Background

The lush bacterial ecosystem in our intestines – referred to as the gut microbiome – has co-evolved with humans to give us the means to efficiently break down food and supply us with extracted energy and nutrients. Beyond its role in digestion, the gut microbiome has a profound impact on health and disease; in particular, researchers have established a link between the gut microbiome and multiple sclerosis. Our gut microbiome helps to calibrate our immune systems, and a growing body of evidence suggests that disturbances in gut microbiome balance can affect the behaviour of immune cells and trigger inflammation, in turn leading to the development of MS in genetically susceptible individuals.

Emerging research has demonstrated that the composition of the gut microbiome in people living with MS is significantly altered compared to healthy people, but important questions about how exactly this leads to MS remain. There is an especially urgent need to study the composition of the gut microbiome in children living with MS, since the gut microbiome is thought to play a fundamental role in immune development during childhood.

A new collaborative research study is now underway to fill this gap in our knowledge. This study, led by Dr. Helen Tremlett (University of British Columbia) and funded by the MS Scientific Research Foundation, will explore the role of the gut microbiome in children living with MS in partnership with a recently launched multi-centre, collaborative pediatric MS study led by Dr. Brenda Banwell (The Hospital for Sick Children and The Children’s Hospital of Philadelphia), who heads the Canadian Pediatric Demyelinating Disease Network. This study will also leverage access to the cohort of participants from the United States Network of Pediatric MS Centers, led by Dr. Emmanuelle Waubant (University of California San Francisco). This unique collaboration between Dr. Tremlett’s research program, the Canadian Pediatric Demyelinating Disease Network and the US Network of Pediatric MS Centers will help to drive large scale advances in research that will ultimately benefit both children and all people living with MS.

The Study

Dr. Tremlett’s study, entitled “From bugs to brains: the gut microbiome in paediatric multiple sclerosis”, will carry out four important objectives:

  • Collect and bank stool samples from children and adolescents enrolled in the pediatric MS study and create a microbiome repository and databank that will be available for future access by other researchers.
  • Catalogue the composition and diversity of both bacteria (microbiome) and viruses (virome) from youth living with MS who have not yet been exposed to immune-modifying therapies, compared to healthy youth. This aim will also explore how certain factors – such as diet, genetics, vitamin D levels, etc. – affect the composition of the gut microbiome.
  • Determine how the microbial communities in the gut function in relation to the body using an advanced computational approach (i.e. what are they capable of doing in youth living with MS?). This will identify genes expressed by the microbes involved in specific metabolic pathways, and link them to features of the immune system involved in the MS disease process.
  • Map out the timeline of the interaction between the gut microbiome and MS disease activity (including relapses and brain lesions) in order to answer the question, “Are any of the changes to the gut microbiome in youth living with MS a cause or consequence of the disease?”

Methods

In order to carry out these aims, the investigators will collect, store and examine stool samples (which are teeming with microbes that make up the communities residing in the gut) from participants in the Canadian collaborative pediatric MS study, including 40 youth with new onset MS, 84 with established MS, and 120 healthy individuals. Samples will also be collected and analyzed from participants in the US Network of Pediatric MS Centers, including 75 youth with MS and 75 healthy individuals.

The group of specialists conducting the study come from diverse fields – including gut microbiome experts, biobank specialists, computational analytics experts, population health researchers and pediatric MS specialists – and will use advanced computational approaches and complex statistical modeling to characterize the genetic makeup of the microbes residing in the gut and link those characteristics to key facets of pediatric MS, including potential triggers or drivers of the disease.

Comment

Examining the gut microbiome in children and adolescents with MS offers researchers a critical window in which to study MS during the earliest stages of the disease. Because children in general have had fewer environmental and lifestyle exposures in life compared to adults, including exposure to diets, infections and so on, this study will provide a unique opportunity to identify possible triggers of MS. Identifying triggers and drivers of the disease, in turn, has the potential to benefit all people with MS or at risk of developing MS in the future. What sets this study apart in particular is that it will tap into the extensive cohort of participants and vast wealth of knowledge made possible by the Canadian Pediatric Demyelinating Disease Network that represents one of the top initiatives for pediatric MS research in the world.