Neuroprotective effect of both synbiotics and ketogenic diet in a pentylenetetrazol-induced acute seizure murine model

Objective: We aimed to maximize the efficacy of both ketogenic diet (KD) and other treatments to protect brain from acute seizure. Methods: L. fermentum MSK 408 strain, galactooligosaccharide (GOS), and L. fermentum MSK 408 with GOS were administered with two different diets for 8 weeks. To reveal the relationships among gut microbiota, fecal short-chain fatty acids (SCFAs) and brain related action against pentylenetetrazole (PTZ)-induced kindling, qPCR, NGS, and GC–MS analyses were used. Results: KD administration significantly reduced PTZ-induced seizure through reducing cell damage in the specific part of the brain; this effect was not interrupted by co-administration of synbiotics. Additionally, the synbiotic-treated normal diet (ND) group showed reduced seizure-related scores. SCFA concentrations of both KDs and ND with synbiotics (NDS) were dramatically reduced compared to those with NDs. Interestingly, NDS group showed independently different SCFAs ratios compared to both ND and KD group, possibly related to a reduction in seizure symptoms compared with that by KD groups. The gut microbiota modulation by KD suggested that the gut microbiota aids the host in generating energy, thus increase the usage of SCFAs such as butyrate and acetate. Significance: The results suggest that KD could reduce PTZ-induced seizures through modulating various factors such as the neuroendocrine system, brain protection, gut microbiota, fecal SCFAs, and gene expression in the gut and brain. Additionally, synbiotic treatment with KD could be a better method to reduce the side effects of KD without interrupting its anti-seizure effect. However, ND with synbiotics seizure reducing effect requires further analysis.