A Ketogenic Diet Affects Gut Microbiota by Regulating Gut Microbiota and Promoting Hippocampal TRHR Expression to Combat Seizures

With the persistent challenge that epilepsy presents to therapeutic avenues, the study seeks to decipher the effects of the ketogenic diet (KD) on gut microbiota and subsequent epileptic outcomes. Mouse fecal samples from distinct KD and control diet (CD) cohorts underwent 16S rRNA sequencing. Differential genes of epileptic mice under these diets were sourced from the GEO database. The study melded in vivo and in vitro techniques to explore the nuanced interactions between KD, gut microbiota, and hippocampal TRHR dynamics. The KD regimen was found to result in a notable reduction in gut microbiota diversity when compared to the CD groups. Distinctive microbial strains, which are hypothesised to interact with epilepsy through G protein-coupled receptors, were spotlighted. In vivo, explorations affirmed that gut microbiota as central to KD’s anti-epileptic efficacy. Of 211 distinguished genes, the neuroactive ligand-receptor interaction pathway was underscored, particularly emphasizing TRHR and TRH. Clinical observations revealed a surge in hippocampal TRHR and TRH expressions influenced by KD, mirroring shifts in neuronal discharges. The KD, leveraging gut microbiota alterations, amplifies hippocampal TRHR expression. This finding provides a novel intervention strategy to reduce seizures.