TARGETING GUT MICROBIOTA COUNTERACTS HIGH-FAT DIET–DRIVEN BEHAVIOURAL AND MOTOR ALTERATIONS IN EAE MICE

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system that leads to motor deficits and sickness behaviour, moving from anxious-depressive phenotype to cognitive impairments. Gut dysbiosis is commonly associated with MS and can be exacerbated by obesity and a high-fat diet (HFD), significantly impacting disease course. Our study aims to investigate the impact of HFD in the MS mouse model Experimental Autoimmune Encephalomyelitis (EAE), on cognitive/behavioural symptoms, and the possible association with the exacerbated gut dysbiosis.
Female-C57BL/6 mice were fed a standard diet (SD, 10% kcal-fat) or HFD (45% kcal-fat) starting 3 weeks prior to EAE MOG35–55 induction. To modulate microbiota, we applied a biphasic prebiotic (2′-fucosyllactose) and probiotic (Saccharomyces boulardii, Lactobacillus, Bifidobacterium; 2×10^8 CFU/day/animal) supplementation (Pre-Pro). The effects of HFD and pre-pro administration were evaluated during the pre-symptomatic phase of the disease (8-10 dpi) to exclude the influence of disability on the behavioural assessment using the following behavioural tests: Open Field Test (OFT), Light-Dark Test (LDT), and Elevated Plus Maze (EPM) to assess anxiety-like phenotype; Forced Swimming Test (FST) to assess the depressive-like phenotype; Novel Object Recognition (NOR) to assess cognitive behaviour. The animals were monitored daily and assigned a clinical score (0 to 5) that represented the severity of motor deficits.
Importantly, we observed that Pre-Pro supplementation improves behavioural and motor deficits in both EAE HFD and SD conditions. Overall, our findings reveal how the microbiota impacts the progression and manifestation of the disease, highlighting Pre-Pro as a promising therapeutic strategy.