Background: Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system with an increasing global incidence rate. Previous studies demonstrated the linkage between inadequate dietary fibre intake and dysregulation of the immune response. It is believed that dietary fibre interacts with the host microbiome and foster the production of short-chain fatty acids (SCFAs) through the fermentation process, which in turn recruits regulatory T-cells (Tregs) and mediates anti-inflammatory effects. However, the roles of fibre intake in MS remains unclear. In this study, we are investigating how different fibre intake in the diet can regulate immune profiles, gut-microglial composition, and metabolites secretion in EAE, the most used MS preclinical model. We hypothesised that high-fibre (HF) feeding will provoke an anti-inflammatory immune response and ameliorate clinical progression.
Methods: Female C57Bl/6 mice were randomly fed a control (AIN93G pallet), HF (20% cellulose and 20% guar gum) or zero-fibre (ZF, fibre-free AIN93G pallet) content diet with ad-libitum food access for 4 weeks. Next, EAE was induced by immunization with a standard protocol using the myelin-derived peptide MOG. Immune profiles were analysed by flow cytometry at 4-weeks after starting the diet (before immunization) and during EAE (40-days post-EAE-induction). Mice were monitored daily to assess clinical progression.
Results: Immuneprofiling of blood cells and spleen after 4 weeks on the specific diet revealed that percentages of Ly6Chi monocytes (with pro-inflammatory functions) were increased significantly in the HF compared to the ZF group. On the contrary, there was a reduction in the frequency of Tregs in the HF group with a trend of decreased γδT cells in the blood compared to ZF. Following EAE induction, the HF groups showed a delayed onset of clinical EAE, but and overall higher disease severity compared to the ZF group. Further analysis of gene expression in the gut by qPCR, SCFA analysis in the serum by using Nuclear Magnetic Resonance will be conducted.
Conclusions: In conclusion, HF feeding showed a delayed start of EAE neurological signs, a more severe clinical course and higher abundance of circulating pro-inflammatory Ly6Chi monocytes. Further analyses will be required to examine the mechanisms underlying these observations.