Influence of dietary supplementation with two distinct probiotic strains, Bifidobacterium longum R0175 and Lacticaseibacillus rhamnosus JB-1, on seizure susceptibility and valproate response: Behavioral and biochemical studies in mice.

Abstract

OBJECTIVE: Accumulating preclinical and clinical evidence suggests potential beneficial effects of probiotic supplementation in the management of epilepsy. Here, we aimed to investigate the effect of two distinct bacterial strains, Bifidobacterium longum R0175 and Lacticaseibacillus rhamnosus JB-1, on seizure susceptibility, the antiseizure efficacy of sodium valproate, behavioral and neurochemical parameters, and gut metabolomic profiles in mice. METHODS: Mice received daily oral administration of either B. longum R0175 or L. rhamnosus JB-1 for 28 d. Seizure thresholds were assessed using the maximal electroshock seizure threshold (MEST) test, the 6 Hz seizure threshold test, and the intravenous (iv) pentylenetetrazole (PTZ) seizure test. The efficacy of sodium valproate was evaluated in the subcutaneous (sc) PTZ seizure test. Additional assessments included anxiety-related behavior, neuromotor functions, brain neurochemical and inflammatory markers, fecal short-chain fatty acids (SCFAs), and untargeted metabolomic profiling of fecal samples. RESULTS: B. longum R0175 and L. rhamnosus JB-1 did not affect the thresholds for tonic seizures in the MEST test and for psychomotor seizures in the 6 Hz test. B. longum R0175 slightly increased the threshold for myoclonic seizures in the ivPTZ. Both strains enhanced the antiseizure efficacy of sodium valproate without altering its serum or brain concentrations. No significant effects were observed on anxiety-related behavior, neuromotor function, neurochemical or inflammatory markers. Both probiotics increased the concentration of butyrate and total SCFAs in fecal samples. Metabolomic analysis revealed variations in the metabolism of bile acids, polyphenols, fatty acids, and amino acids. CONCLUSIONS: The probiotics alone had minimal effects on seizure thresholds, but they enhanced the antiseizure efficacy of valproate, which may be linked to increased SCFA production and altered gut metabolism. These findings support further studies on probiotics as a complementary strategy in epilepsy treatment.