Grant: Travel Awards - Institute Community Support

Objective: A growing body of evidence supports the role of the gut microbiome in regulating diverse physiological processes, including neural, immune, and metabolic functions via the gut-brain axis. Infantile spasms syndrome is an early-onset epilepsy associated with perturbed neuroinflammation and refractory to antiepileptic medication in infants. We have developed a microbiome-based intervention using a defined microbial consortium that confers anti-convulsant protection. However, whether its mechanism of action involves the regulation of neuroinflammation remains unclear. Design: Using a neonatal rat model of infantile epilepsy, the present study evaluated the impact of a microbial consortium (Streptococcus thermophilus and Lactococcus lactis) on peripheral immune responses and neuroinflammation. Key outcomes included seizures, serum cytokine profiles, and hippocampal proteome. Results: While reducing seizure frequency, the microbial consortium markedly altered immune profiles in both the peripheral and central nervous systems. In serum, it lowered the concentrations of inflammatory cytokines, including interleukin-18, interleukin-6, and tumor necrosis factor-a. In the hippocampus, it significantly changed the expression of 944 proteins, notably upregulating those involved in aryl hydrocarbon receptor signaling while downregulating pathways related to chemokine signaling, neuroinflammation, glutamatergic signaling, and neutrophil degranulation, a process that contributes to neuroinflammation through the release of inflammatory mediators. Conclusion: The results demonstrate that the microbiome-based intervention reduces seizure frequency and ameliorates neuroinflammation in a rodent model of infantile epilepsy, providing new insights into microbiota manipulation as a potential therapeutic avenue for pediatric epileptic disorders.