Identifying the Role of the Gut Microbiome in Pediatric Multiple Sclerosis

The gut microbiome are microorganisms, such as bacteria and fungi, that live in the digestive tract. They are believed to play a fundamental role in immune development and regulation of the central nervous system. Hence, researchers are interested in how alterations in the composition of the gut microbiome might influence immune mediated diseases such as multiple sclerosis (MS).

Through the support of the MS Scientific Research Foundation and in collaboration with the Canadian Pediatric Demyelinating Disease Network, Dr. Helen Tremlett (University of British Columbia) and team examined the gut microbiome of children and youth with and without MS to better understand the associations between gut microbiome composition and disease development. While MS in children is rare, this cohort provides an important opportunity to study the disease very close to its onset. Additionally, unlike adults with MS, children have had fewer environmental and lifestyle exposures to different diets, medications, and infections, which provides a unique opportunity for identifying potential triggers of MS.

After analyzing stool samples from 32 MS participants and 36 unaffected controls, Dr. Tremlett’s team found no difference in the diversity or different types of microbes present in the gut of participants with and without MS. However, they did observe differences in the relative numbers or abundance of certain microbial communities between the two groups. In participants with MS, there was an overrepresentation of more harmful microorganisms and an underrepresentation of potentially beneficial microbes that have anti-inflammatory effects1. These findings were further confirmed in a second cohort of children from the US Network of Pediatric MS Centers.

In a follow-on study, the team used an advanced computational approach called metagenomics to determine how the microbial communities of participants with and without MS function based on the types of genes they express. Those with MS had an overrepresentation of microbial genes involved in responding to heavy metals, such as cadmium and arsenic, that are toxic to the brain2. MS participants also showed lower numbers of carbohydrate-degrading proteins in their gut, suggesting that individuals with MS may be depleted of anti-inflammatory compounds that is usually acquired from the diet such as butyrate2,3.

Together, these results suggest that even though the gut microbiome composition of children and youth with and without MS appears to be similar, differences in the relative abundance of microbial communities and differences in their activities may contribute to MS pathogenesis. This work may provide insight on the potential causes of MS as well as factors that might influence the disease in those who already have MS. More research is needed to further understand the role of the gut microbiome in MS.

For more information about the research, click here.

Resources:

1. Tremlett H, et al. The gut microbiota in pediatric multiple sclerosis and demyelinating syndromes. Annals of Clinical and Translational Neurology. 2021;8(12):2252-2269.

2. Mirza A, et al. Metagenomic analysis of pediatric-onset multiple sclerosis gut microbiome. Neurology. 2022;98(10):e1050-e1063.

3. Mirza A, et al. The metabolic potential of the paediatric-onset multiple sclerosis gut microbiome. Multiple Sclerosis and Related Disorders. 2022;63:103829.