Age-related impacts of the intestinal microbiota on multiple sclerosis: defining mechanisms of neurodegeneration

Progressive Multiple Sclerosis (pMS) is a prevalent neurodegenerative illness in Canada. Unfortunately, people living with pMS have limited treatment options. Age is a strong risk factor for MS progression, indicating that biological changes that occur with age could contribute to pMS-related neurodegeneration. All forms of MS show associations with the microbiome, and the microbiome undergoes substantial changes during aging. However, whether age-related changes to the gut microbiota are important contributors to the neurodegeneration seen in pMS remains undefined. Thus, I will perform fecal microbiota transplant (FMT) of samples collected from healthy aged vs young people into microbiota-depleted mice, followed by treatment to induce a laboratory form of MS. This experimental set-up allows me to isolate the role of an aged vs young microbiota on MS outcomes. In preliminary studies, mice harboring an aged microbiome develop pMS-like disease. I will identify specific microbes and the molecules they produce in aged FMT mice that exacerbate neurodegeneration. These studies will lead to better understanding of the mechanisms driving neurodegeneration in pMS, and the identification of new targets for this treatment-resistant disease.