Effects of a Gut Microbiome Toxin, p-Cresol, on the Susceptibility to Seizures in Rats

Several studies have highlighted a high comorbidity between epilepsy and autism. We hypothesized that some similar etiological factors might affect both disorders; among such factors, gut microbiome neurotoxins may participate in the development of these neurological disorders. We found that course (21 day) i.p. injections of a gut microbiome toxin, p-cresol, in genetically epilepsy-prone Krushinski–Molodkina rats led to significantly shorter latent periods of tonico-clonic seizures in response to strong sound stimulation of these animals. Besides, i.p. injection of single doses of p-cresol resulted in 8- to 10-fold prolongation of stimulation-dependent EEG seizure discharges in the hippocampus of Wistar rats. Thus, introduction of p-cresol considerably increases the seizure readiness in rats. These data suggest a possibility of the common mechanism involved in the p-cresol-induced development of both autism and epilepsy.