Viral Infection-Induced Epilepsy and the Gut Microbiome Crosstalk

Viral infections of the central nervous system (CNS) pose a significant risk for seizures, and in some cases, long-term epileptogenesis. Seizure development following viral infection involves diverse CNS mechanisms, with emerging evidence that peripheral factors, including gut microbiome composition and immune-inflammatory responses, also contribute. The gut microbiome is a multifaceted ecosystem with important roles in CNS health, and advances in sequencing have enabled investigation of host and microbial genomic changes associated with seizure development. While both animal and human studies link gut dysbiosis to epilepsy, including infection-induced epilepsy, the specific effects of viral-induced seizures on the gut microbiome remain unclear. Moreover, the influence of virus-triggered epileptogenesis is not well understood. This review summarizes current knowledge on viral infections linked to seizures and highlights the limited but growing evidence for gut microbial changes in this context. We focus on Zika virus (ZIKV), West Nile virus (WNV), and herpes simplex virus-1 (HSV-1), all implicated in human epileptogenesis, though direct microbiome-seizure connections are still limited. We also discuss severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes neurological symptoms without consistently inducing seizures in rodent models despite neurological involvement, and Theiler's murine encephalomyelitis virus (TMEV), a murine virus widely used as a model of infection-induced seizures because it induces strain-dependent seizures in mice. Current evidence suggests associations among viral infections, gut microbiome alterations, and seizure occurrence; however, further causative studies are needed to define their roles and elucidate underlying mechanisms.