Abstract

Abstract Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Studies demonstrated the association between inadequate dietary fibre intake and dysregulation of the immune response, the impact of which in MS remains controversial. Using experimental autoimmune encephalomyelitis (EAE) animal model of MS, this study investigated how dietary fibre regulates adaptive immune cells, gut-microbial composition, and metabolite secretion. Following EAE induction, the high fibre (HF) group showed an earlier onset, higher disease incidence and severity compared to the zero fibre (ZF) group. Immune profiling of peripheral blood cells and splenocytes after 5-weeks on the HF diet revealed a pro-inflammatory immune phenotype, with increased numbers of pro-inflammatory Ly6C himonocytes and decreased numbers of anti-inflammatory IL-10 +CD4 +T-cells and T-regs the spleen compared to the ZF-fed mice. Short chain fatty acids (SCFAs) measurements at 5-weeks on the diet, showed a global increase of acetate, propionate and butyrate concentrations in the HF group compared to ZF cohorts. After EAE induction, Ly6C himonocytes were decreased peripherally, while there was an increased number of dendritic cells and infiltration of monocytes in CNS in the HF compared to the ZF group. In conclusion, a HF diet was associated with a more pro-inflammatory systemic profile and a worse EAE clinical course. This is likely due to the complex biology of SCFAs, which could have pro- or anti-inflammatory effects depending on the context of immune cell activation. Further research is needed to clarify these mechanisms. Starter funding support

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