Microbiome depletion by broad-spectrum antibiotics does not influence demyelination and remyelination in cuprizone-treated mice

Demyelination in the central nervous system (CNS) is a feature of various psychiatric and neurological disorders. Emerging evidence suggests that the gut-brain axis may play a crucial role in CNS demyelination. The cuprizone (CPZ) model, which involves the administration of CPZ-containing food pellets, is commonly used to study the effects of different compounds on CNS demyelination and subsequent remyelination. This study aimed to evaluate the impact of microbiome depletion, induced by an antibiotic cocktail (ABX), on demyelination in CPZ-treated mice and the subsequent remyelination following CPZ withdrawal. Our findings indicate that a chronic 4-week oral ABX regimen, administered both during and after a 6-week CPZ exposure, does not affect demyelination or remyelination in the brains of CPZ-treated mice. Specifically, ABX treatment for 2 weeks before and 2 weeks after CPZ exposure, in the final 4 weeks before sacrifice, and for 4 weeks post-CPZ withdrawal, did not significantly alter these processes compared to control mice receiving water instead of ABX. These results indicate that despite effective microbiome depletion, a 4-week oral ABX regimen does not influence demyelination or remyelination in the CPZ model. Thus, it is unlikely that gut microbiota depletion by ABX plays a significant role in these processes. However, further research is needed to fully understand the role of the host microbiome on CPZ-induced demyelination.