Portugal 2023 Portuguese Grant Winner

Multiple Sclerosis is a chronic autoimmune neurodegenerative disease and the major cause of non-traumatic neurological disability. Despite it affects mainly young adults, the older onset age is a predictor of worse relapse episodes with a faster progressive course and loss of therapeutic efficacy.

Multiple Sclerosis patients, despite neurodegenerative symptomatology, also display neuropsychiatry deficits (i.e. cognitive impairment, anxiety and depression) that greatly impact disease progression and pathogenesis. Previous studies revealed that, in the in vivo model of Multiple Sclerosis, age is a predictor of worse disease progression accompanied with a higher accumulation of health deficits measured by the frailty index. Moreover, the relevance of the interaction between the gut microbiome and the central nervous system in autoimmune disorders such as Multiple Sclerosis is only now being clarified using animal and clinical studies. However, how age may alter microbiome composition and therefore impact the emergence of disease psychopathology symptoms is still a gap to fill, further questioning the potential of gut microbiome modulation in ameliorating disease progression.

In this project, we will modulate the gut microbiome of a middle-aged mouse model of Multiple Sclerosis using specific fecal transplantation from young naïve mice to assess the amelioration of disease pathogenesis and psychopathology symptoms. We expect to see an improvement in the disease symptoms and prevention of disease pathogenesis, which can be a first step into clinical translation to improve the quality of life of Multiple Sclerosis patients or even delay or stop disease evolution to a more progressive phase.