Infantile spasms syndrome (IS) is a devastating early-onset epileptic
encephalopathy associated with poor neurodevelopmental outcomes. When first-line treatment options, including
adrenocorticotropic hormone and
vigabatrin, are ineffective, the
ketogenic diet (KD) is often employed to control
seizures. Since the therapeutic impact of the KD is influenced by the gut microbiota, we examined whether targeted microbiota manipulation, mimicking changes induced by the KD, would be valuable in mitigating
seizures. Employing a rodent model of symptomatic IS, we show that both the KD and
antibiotic administration reduce
spasm frequency and are associated with improved developmental outcomes.
Spasm reductions were accompanied by specific gut microbial alterations, including increases in Streptococcus thermophilus and Lactococcus lactis. Mimicking the fecal microbial alterations in a targeted probiotic, we administered these species in a 5:1 ratio. Targeted probiotic administration reduced
seizures and improved locomotor activities in control diet-fed animals, similar to KD-fed animals, while a negative control (Ligilactobacillus salivarius) had no impact. Probiotic administration also increased
antioxidant status and decreased proinflammatory
cytokines. Results suggest that a targeted probiotic reduces seizure frequency, improves locomotor activity in a rodent model of IS, and provides insights into microbiota manipulation as a potential therapeutic avenue for pediatric epileptic
encephalopathies.